Charged particle trapping in near-surface potential wells

ABSTRACT

A Time-Of-Flight mass spectrometer is configured with a pulsing region and electronic controls that generate a potential well for ions in the pulsing region, due to the repelling effect of a high-frequency electric field that is created in the space immediately proximate to a surface, and an additional static electric field that accelerates ions toward the surface. Ions can be constrained and accumulated over time in the potential well prior to acceleration into the Time-Of-Flight tube for mass analysis. Ions can also be directed to collide with the surface with high energy to cause Surface Induced Dissociation (SID) fragmentation, or with low energy to effect collisional cooling, hence, better spatial focusing, prior to mass analysis. The apparatus and methods described in the invention result in refined control of ion fragmentation energy and improved Time-Of-Flight mass analysis performance.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 60/264,856 filed Jan. 29, 2001.

FIELD OF THE INVENTION

The present invention relates to the field of mass spectrometry and inparticular to apparatus and methods for the interaction of ions withcombined high frequency and static electric fields near surfaces.

BACKGROUND OF THE INVENTION

Mass spectrometers are used to analyze sample substances containingelements or compounds or mixtures of elements or compounds by measuringthe mass to charge of ions produced from a sample substance in an ionsource. A number of types of ion sources that can produce ions fromsolid, liquid or gaseous sample substrates have been combined with massspectrometers. Ions can be produced in vacuum using ion sources,including, but not limited to, Electron Ionization (EI), ChemicalIonization (CI), Laser Desorption (LD), Matrix Assisted LaserDesorption, (MALDI), Fast Atom Bombardment (FAB), Field Desorption (FD)or Secondary Ion Mass Spectrometry (SIMS). Alternatively, ions can beproduced at or near atmospheric pressure using ion sources, including,but not limited to, Electrospray (ES), Atmospheric Pressure ChemicalIonization (APCI) or Inductively Coupled Plasma (ICP). Ion sources thatoperate at intermediate vacuum pressures such as Glow Discharge IonSources have also been used to generate ions for mass spectrometricanalysis. Ion sources that operate in vacuum are generally located inthe vacuum region of the mass spectrometer near the entrance to the massanalyzer to improve the efficiency of ion transfer to the detector. Ionsources that produce ions in vacuum have also been located outside theregion near the mass spectrometer entrance. The ions produced in alocation removed from the mass analyzer entrance must be delivered tothe entrance region of the mass spectrometer prior to mass analysis.Atmospheric or intermediate pressure ion sources are configured todeliver ions produced at higher pressure into the vacuum region of themass analyzer. The geometry and performance of the ion optics used totransport ions from an ion source into the entrance region of a givenmass analyzer type can greatly affect the mass analyzer performance.This is particularly the case with Time-Of-Flight mass analyzers, inwhich the initial spatial and energy distribution of the ions pulsedinto the flight tube of a Time-Of-Flight mass analyzer affects theresulting mass to charge analysis resolving power and mass accuracy.

Mass analysis conducted in a Time-Of-Flight mass (TOF) mass spectrometeris achieved by accelerating or pulsing a group of ions into a flighttube under vacuum conditions. During the flight time, ions of differentmass to charge values spatially separate prior to impacting on adetector surface. Ions are accelerated from a first acceleration orpulsing region and may be subject to one or more acceleration anddeceleration regions during the ion flight time prior to impinging on adetector surface. Multiple ion accelerating and decelerating stagesconfigured in Time-Of-Flight mass spectrometers aid in compensating orcorrecting for the initial ion spatial and energy dispersion of theinitial ion population in the first ion pulsing or accelerating region.The most common lens geometry used in the first TOF ion pulsing oraccelerating region is two parallel planar electrodes with the electrodesurfaces oriented perpendicular to the direction of ion accelerationinto the Time-Of-Flight tube. The direction of the initial ionacceleration is generally in a direction parallel with the TOF tubeaxis. A linear uniform electric field is formed in the gap between thetwo parallel planar electrodes when different electrical potentials areapplied to the two electrodes. The planar electrode positioned in thedirection of ion acceleration into the TOF tube is generally configuredas a highly transparent grid to allow ions to pass through with minimalinterference to the ion trajectories. To maximize the performance of aTime-Of-Flight mass analyzer, it is desirable to initiate theacceleration of ions in the pulsing region with all ions initiallypositioned in a plane parallel with the planar electrodes and initiallyhaving the same initial kinetic energy component in the direction ofacceleration. Consequently, when ions are generated in or transportedinto the initial accelerating or pulsing region of a Time-Of-Flight massanalyzer, conditions are avoided which lead to ion energy or spatialdispersion at the initiation of ion acceleration into the Time-Of-Flighttube drift region. As a practical matter, a population of gaseous phaseions located in the pulsing region will have a non-zero spatial andkinetic distribution prior to pulsing into a Time-Of-Flight tube driftregion. This non zero spatial and kinetic energy spread may degradeTime-Of-Flight mass to charge analysis resolving power, sensitivity andmass measurement accuracy. In one aspect of the present invention, thespatial and energy spread of an ion population is minimized prior toaccelerating the population of ions into a Time-Of-Flight tube driftregion.

When ion spatial and energy spread can not be avoided in the TOF pulsingor first accelerating region, it is desirable to have the ion energy andspatial distributions correlated so that both can be compensated andcorrected for during the ion flight time prior to hitting the detector.A correlation between the ion kinetic energy component in the TOF axialdirection and spatial spread can occur in the TOF pulsing region whenspatially dispersed ions with a non random TOF axial kinetic energycomponent are accelerated in a uniform electric field formed between twoparallel electrodes. Wiley et. al., The Review of Scientific Instruments26(12):1150-1157 (1955) described the configuration and operation of asecond ion accelerating region to refocus ions of like mass to chargealong the TOF flight path that start their acceleration with acorrelated spatial and energy spread. Electrode geometries in the TOFtube and voltages applied to these electrodes can be varied with thistechnique to position the focal plane of a packet of ions of the samemass to charge value at the detector surface to achieve maximumresolving power. The Wiley-McClaren focusing technique improvesresolving power when ions occupying a finite volume between two parallelplate electrodes are accelerated. In a uniform electric acceleratingfield, ions of the same m/z value located closer to the repellingelectrode will begin their acceleration at a higher potential than anion of the same m/z initiating its acceleration at a position furtherfrom the repelling electrode. The ion that starts its accelerationnearer to the repelling electrode surface at a higher potential, musttravel further than the slower ion which starts its acceleration at alower potential closer to the extraction grid or electrode. At somepoint in the subsequent ion flight, the faster ion will pass the slowerion of the same m/z value. By adding a second accelerating region, thelocation of the point where the ions having the same mass to chargevalue pass and hence are “focused” in a plane, can be optimized toaccommodate a desired flight time and flight tube geometry. The focalpoint occurring in the first field free region in the TOF drift tube canbe “reflected” into a second field free region using an ion mirror orreflector in the ion flight path.

Variations in ion flight time can also be caused by initial ion velocitycomponents not correlated to the spatial spread. This non-correlated ionkinetic energy distribution can be compensated for, to some degree, bythe addition of an ion reflector or mirror in the ion flight path. Ionsof the same m/z value with higher kinetic energy in the TOF axialdirection will penetrate deeper into the decelerating field of an ionreflector prior to being re-accelerated in the direction of thedetector. The ion with higher kinetic energy experiences a longer flightpath when compared to a lower energy ion of the same m/z value.Subjecting an ion to multiple accelerating and decelerating electricfields allows operation of a TOF mass analyzer with higher orderfocusing to improve resolving power and mass measurement accuracy.Configuration and operation of an Atmospheric Pressure Ion SourceTime-Of-Flight mass analyzer with higher order focusing is described byDresch in U.S. Pat. No. 5,869,829. Higher order focusing corrections cannot entirely compensate for initial ion kinetic energy spread in the TOFaxial direction that is not correlated with ion spatial spread in theinitial pulsing or ion acceleration region. Also, higher order focusingcan not entirely compensate for ion energy or spatial spreads whichoccur during ion acceleration, deceleration or field free flight due toion fragmentation or ion collisions with neutral background molecules.An ion kinetic energy distribution not correlated to the ion spatialdistribution can occur when ionization techniques such as MALDI areused. In MALDI ionization, the sample-bearing surface is located in theinitial acceleration region of a Time-Of-Flight mass spectrometer. Alaser pulse impinging on a sample surface, in a MALDI ion source,creates a burst of neutral molecules as well as ions in the initialaccelerating region of a Time-Of-Flight mass analyzer. Ion to neutralmolecule collisions can occur during ion extraction and accelerationinto the TOF drift tube resulting in an ion kinetic energy spread, ionfragmentation, degradation of resolving power and errors in mass tocharge measurement. This problem increases if structural information viaion fragmentation is desired using MALDI Time-Of-Flight mass analysis.Higher energy laser pulses used in MALDI to increase the ionfragmentation also result in increased neutral molecule ablation fromthe target surface. Even in the absence of ion-neutral collisions, ionsgenerated from the target surface have an initial velocity or kineticenergy distribution that is not well correlated to spatial distributionin the first ion acceleration region. This initial non-correlatedkinetic distribution of the MALDI generated ion population can degraderesolving power, and mass accuracy performance in Time-Of-Flight massanalysis.

A technique, termed delayed extraction, has been developed where theapplication of an electric field to accelerate ions into the TOF drifttube is delayed after the MALDI laser pulse is applied to allow time forthe neutral gas to expand, increasing the mean free path prior to ionacceleration. By applying a small reverse accelerating field during theMALDI laser pulse and delaying the acceleration of ions into theTime-Of-Flight tube drift region, as described by Vestal et. al. in U.S.Pat. No. 5,625,184, some portion of the low m/z ions can be eliminated.A portion of the low m/z ions, primarily matrix related ions, created inthe MALDI process are accelerated back to the sample surface andneutralized when the reverse electric field is applied. A portion of theslower moving higher mass to charge ions do not return to the targetsurface as rapidly as the lower molecular weight ions when the reverseaccelerating field is applied. After an appropriate delay, these highermolecular weight ions may be forward accelerated into the TOF tube driftregion by switching the electric field applied between the twoelectrodes in the first ion acceleration region. Delayed extraction alsoallows many of the ion fast fragmentation processes to occur prior toaccelerating ions into the Time-Of-Flight tube drift region, resultingin improved mass to charge resolving power and mass accuracymeasurements for the ions produced in fast fragmentation processes. Thedelayed extraction technique reduces the ion energy deficit which canoccur due to ion-neutral collisions in the first accelerating region butdoes not entirely eliminate it, particularly with higher energy laserpulses. Also, delayed extraction is effective in improving MALDITime-Of-Flight performance when lasers with longer pulse durations areused. However, even with delayed extraction, there is a limit to thelength of delay time, the magnitude of the reverse field during thedelay period, the laser power used and the duration of a laser pulsebefore overall sensitivity or Time-Of-Flight performance is degraded.The delayed extraction technique requires a balancing of severalvariables to achieve optimal performance, often with compromises to theTime-Of-Flight mass analysis performance over all or some portion of themass to charge spectrum generated. The present invention improves theperformance of MALDI Time-Of-Flight without imposing the restrictions orlimitations of conventional delayed extraction techniques and providesmore uniform Time-Of-Flight mass analysis performance over a wider massto charge range.

When ions are generated in an ion source positioned external to theTime-Of-Flight pulsing or first acceleration region, a technique termed“orthogonal” pulsing has been used to minimize effects of the kineticenergy distribution of the initial ion beam. This orthogonal pulsingtechnique first reported by The Bendix Corporation Research LaboratoriesDivision, Technical Documentary Report No. ASD-TDR-62-644, Part 1, April1964, has become a preferred technique to interface external ionsources, particularly Atmospheric Pressure Ionization Sources, withTime-Of-Flight mass analyzers. The ion beam produced from an AtmosphericPressure Ion Source (API) or an ion source that operates in vacuum, isdirected into the gap between the two parallel planar electrodesdefining the first accelerating region of the TOF mass analyzer. Theprimary ion beam trajectory is directed to traverse the gap between thetwo parallel planar electrodes in the TOF first accelerating regionsubstantially orthogonal to the axis of the direction of ionacceleration into Time-Of-Flight tube. When orthogonal pulsing is used,ion kinetic energy in the primary ion beam direction is not coupled tothe ion velocity component oriented in the direction of ion accelerationinto the Time-Of-Flight tube drift region. The primary ion beam kineticenergy spread oriented along the beam axis only affects the location ofion impact on the planar detector surface, not the ion arrival time atthe detector surface. Apparatus and methods have been developed toimprove the duty cycle of TOF mass analyzers configured with linear ororthogonal pulsing geometries.

Grix, et. al., in Int. J. Mass Spectrom. Ion Processes 93, 323 (1989)describe an approach for creating and storing ions in the TOF pulsingregion between extraction pulses. Sample gas is introduced directly intothe TOF pulsing region, and an election beam is directed to pass throughthe TOF pulsing region, which ionizes sample gas molecules. The electionbeam is sufficiently intense so that the local potential well producedby the electrons traps a substantial number of ions until they arepulsed into the TOF drift region for mass analysis. Severaldisadvantages of this approach include: 1) sample gas is introduceddirectly into the TOF optics, degrading the vacuum and causing ionscattering; 2) electron impact ionization results in substantialfragmentation which renders this ionization method impractical for massanalysis of many types of samples, such as large biomolecules; and 3)the sample needs to be introduced into the TOF as a gas, which makesthis approach incompatible with non-volatile samples.

Chien, et. al., in Anal. Chem. 66, 1630 (1994), and references therein,describe a configuration which incorporates a Paul three-dimensionalRF-quadrupole ion trap as the TOF pulsing region for the TOF massanalysis of ions generated externally by MALDI and by electrosprayionization. Ions can be accumulated in such a trap prior to pulsing theions out of the trap and into the TOF drift region. However, thecontinuous transfer of externally-generated ions into such athree-dimensional RF-quadrupole ion trap is problematic because ionswith energies great enough to overcome the RF-fields in the trap andenter the trap will generally have too much energy to be trapped oncethey are in the trap volume. Therefore, complicated schemes are employedwith limited success to overcome this difficulty, such as pulsing orramping the RF voltages on and off in concert with pulsed ionintroduction; synchroniziing pulsed ion introduction with the phase ofthe RF waveform; and/or introducing inert gas with which the ions cancollide and dissipate kinetic energy during ion trapping. Anotherdisadvantage of this configuration is that the electrode geometry thatcreates the trapping fields is unable to create the linear fields duringthe pulsed TOF acceleration necessary for achieving maximum TOF massresolving power.

Ji. et. al., J. Amer. Soc. Mass Spec. 7, 1009 (1996) describe athree-dimensional planar electrode ion trap configured as the pulsingregion of a TOF mass spectrometer. Their approach was to ionize andcollect ions directly in the trap by electron-impact ionization ofgaseous sample molecules introduced into the trap, and then to pulse thetrapped ions into the TOF drift region for mass analysis. This ionoptics arrangement is able to produce improve TOF accelecration fieldsrelative to those produced by typical three-dimensional ion traps withcurved electrode surfaces. However, a three-dimensional planar-electrodeion trap employed as the pulsing region of a TOF mass spectrometersuffers from difficulties in efficient trapping of ions due to thenon-ideal trapping fields, as well as from scattering of ions by thesample gas and by the gas introduced to collisionally cool the ions inthe trap, which degrades TOF mass resolution and sensitivity. Dresch etal. in U.S. Pat. No. 5,689,111 describe an apparatus and method forimproving the duty cycle and consequently the sensitivity of aTime-Of-Flight mass analyzer. Ions contained in a continuous ion beamdelivered from an atomspheric pressure ion source into a two-dimensionalmultipole ion guide, are trapped in the multipole ion guide andselectively released from the ion guide exit into the TOF pulsingregion. This apparatus and technique delivers ion packets into thepulsing or first acceleration region of a TOF mass analyzer from acontinuous ion beam with higher efficiency and less ion loss than can beachieved with a continuous primary ion beam delivered directly into theTOF pulsing region. Ion trapping of a continuous ion beam in an ionguide effectively integrates ions delivered in the primary ion beambetween TOF pulses. When this apparatus and technique is applied to anorthogonal pulsing TOF geometry, portions of the mass to charge rangecan be prevented from being accelerated into the Time-Of-Flight driftregion, reducing unnecessary detector channel dead time, resulting inimproved sensitivity and dynamic range. Operation with the orthogonalpulsing technique has provdied significant Time-Of-Flight mass analysisperformance improvements when compared with the performance usingin-line ion beam pulsing techniques.

Frazen in U.S. Pat. No. 5,763,878 describes a multipole ion guide thatextends orthogonally into the pulsing region of a TOF mass spectrometer.Ion can be transported from an external ion source into the TOF pulsingregion located within a portion of the length of the ion guide, andaccelerated orthogonally into the TOF drift region by applying pulsedacceleration voltages to the multipole rods so as to accelerate the ionsthrough the space between two of the rods. One disadvantage of thisscheme is that linear acceleration fields required for optimum TOF massresolving power could not be formed by the inhomogeneous accelerationfields produced by such a multipole rod stucture.

Even with orthogonal injection of ions into a pulsed acceleration regionwith perfectly planar fields, it is not always possible to achieveoptimal primary ion beam characteristics in the pulsing region wherebyall orthogonal velocity components are eliminated or spatiallycorrelated. An approach intended to overcome such limitations has beendescribed by Whitehouse, et. al., in U.S. Pat. No. 6,040,575. Oneembodiment of their invention combines orthogonal ion beam introductioninto the TOF pulsing region with ion collection on a surface prior topulsing the surface collected ion population into the TOF tube driftregion. The spatial and energy compression of the ion population on thecollecting surface prior to pulsing into the TOF tube drift regionimproves the Time-Of-Flight mass resolving power and mass accuracy.Their invention also results in improved sensitivity by collecting andstoring ions between TOF acceleration pulses that would have beenotherwise lost. Further, surface induced dissociation (SID) andsubsequent collection, storage, and TOF mass analysis of the resultingfragment ion population is facilitated by directing ions to impact thecollecting surface with high energy. However, their approach ispractical only if the interaction between the ions and the surface isweak enough so that: 1) the charge on the ions is maintained; 2) the“sticking probability” for the ions on the surface is high enough tocapture and hold ions, but low enough to allow the ions to be desorbedintact and without impedance upon application of the acceleration pulseof the time of flight analyzer, possibly with the assistance of someauxiliary desorption process, such as the application of heat, an ionbeam pulse, or a laser pulse; and 3) the deposition and desorptionprocesses can be cycled repetitively many times without substantialdegradation of the surface characteristics.

One embodiment of the present invention involves ion collection ofexternally generated ions in an ion trap in the pulsed accelerationregion, but rather than collecting ions on a surface, or in thethree-dimensional pseudo potential energy well of a typicalthree-dimensional RF-ion trap, ions are collected instead in apseudo-potential energy well that is primarily one-dimensional, with thepseudo potential well axis oriented parallel to the flight tube axis,prior to pulsing the collected ion population into the TOF tube driftregion. The resulting constraints on the spatial and energydistributions of the ion population prior to pulsing into the TOF driftregion improves Time-Of-Flight performance and analytical capability.Further, by allowing the ions to gently collide with the surface or withan inert gas, the spatial and energy distributions of the ion populationcollected in the one-dimensional pseudo-potential energy well can becompressed, resulting in additional improvement in Time-Of-Flightperformance and analytical capability.

The orthogonal pulsing technique has been configured in hybrid or tandemmass spectrometers that include Time-Of-Flight mass analysis. Two ormore individual mass analyzers are combined in tandem or hybrid TOF massanalyzers to achieve single or multiple mass to charge selection andfragmentation steps followed by mass analysis of the product ions.Identification and/or structural determination of compounds is enhancedby the ability to perform MS/MS or multiple MS/MS steps (MS/MS″) in agiven chemical analysis. It is desirable to control the ionfragmentation process so that the required degree of fragmentation for aselected ion species can be achieved in a reproducible manner.Time-Of-flight mass analyzers have been configured with magnetic sector,quadrupole, ion trap and additional Time-Of-Flight mass analyzers toperform mass selection and fragmentation prior to a final Time-Of-Flightmass analysis step. Gas phase Collisional Induced Dissociation (CID) andSurface Induced Dissociation (SID) techniques have been used toselectively fragment gas phase ions prior to TOF mass analysis or havebeen coupled to the ion flight path in the Time-Of-Flight tube. CID ionfragmentation has been the most widely used of the two techniques.Magnetic sector mass analyzers have been configured to perform mass tocharge selection with higher energy CID fragmentation of mass to chargeselected ions to aid in determining the structure of compounds. Lowerenergy CID fragmentation achievable in quadrupoles, ion traps andFourier Transform mass analyzers, although useful in many analyticalapplications, may not provide sufficient energy to effectively fragmentall ions of interest. High energy CID fragmentation can yield side chaincleavage fragment ion types such as w type fragments. This type offragmentation is less common in low energy CID processes. The additionalion fragmentation information achievable with higher energyfragmentation techniques can be useful when determining the structure ofa molecule.

An alternative to CID ion fragmentation is the use of Surface InducedDissociation to fragment ions of interest. The capability of the SurfaceInduced Dissociation ion fragmentation technique has been reported for anumber of mass analysis applications. Wysocki et. al. J. Am. Soc. forMass Spec., 1992, 3, 27-32 and McCormack et. al., Anal. Chem. 1993, 65,2859-2872, have demonstrated the use of SID ion fragmentation withquadrupole mass analysis to controllably and reproducibly achieveanalytically useful fragmentation information. McCormack et. al. showedthat with collisional energies below 100 eV, w and d type ion fragmentscan be produced from some peptides. Kiloelectronvolt gas phasecollisions may be required to achieve similar ion fragmentation. Higherinternal energy transfer to an ion can be achieved in SID than with gasphase CID processes allowing the possibility of fragmenting large ions,even those with a large number of degrees of freedom and low numbers ofcharges. Also, the ion collisional energy distributions can be moretightly controlled with SID when compared with gas phase CID processes.A variety of collision surfaces have been used in SID experimentsranging from metal conductive surfaces such as copper and stainlesssteel to self-assembled alkyl-monolayer surfaces such asoctadecanethiolate (CH3(CH2)17SAu), ferrocence terminated self assembledalkyl-monolayer surfaces and fluorinated self-assembled monolayer(F-SAM) surfaces (CF3(CF2)7(CH2)2 SAu). The self-assembled monolayersurfaces tend to reduce the charge loss to the surface during the SIDprocess. Winger et. al. Rev. Sci. Instrum., Vol 63, No. 12, 1992 havereported SID studies using a magnetic sector-dual electricsector-quadrupole (BEEQ) hybrid instrument. They showed kinetic energydistributions of up to ±3 eV for parent and fragment ions leaving aperdeuterated alkyl-monolayer surface after a 25 eV collision. SIDcollisions have been performed by impacting ions traversing aTime-OF-Flight flight tube onto surfaces positioned in the flight tubeand Time-OF-Flight mass to charge analyzing the resulting ionpopulation. Some degree of mass to charge selection prior to SIDfragmentation has been achieved by timing the deflection of ions as theinitial pulsed ion packet traverses the flight tube. SID surfaces havebeen positioned in the field free regions and at the bottom of ionreflector lens assemblies in TOF mass analyzers. The resulting TOF massspectra of the SID fragment ions in these instruments generally have lowresolving power and low mass measurement accuracy due in part to thebroad energy distributions of the SID fragment ions leaving the surface.A population of ions acquiring a kinetic energy spread during its flightpath or during a re-acceleration step in an ion reflector degrades TOFperformance. One embodiment of the present invention reduces the broadkinetic energy distributions of ions produced by SID fragmentation priorto conducting Time-Of-Flight mass analysis. In the present invention,one or more steps of ion mass to charge selection and CID fragmentationcan be conducted prior to performing a SID fragmentation step in the TOFpulsing region.

The present invention relates to the configuration and operation of aTime-Of-Flight mass analyzer in a manner that results in improved TOFperformance and range of TOF analytical capability. Ions produced froman ion source are directed to a region that contains a pseudo potentialenergy well located in the pulsing or first acceleration region of aTime-Of-Flight mass analyzer prior to accelerating the ions into theTime-Of-Flight tube drift region. Ions in a wide range of mass-to-chargemay be trapped and collected in the pseudo potential well prior toaccelerating the collected ions into the Time-Of-Flight drift tuberegion. Such trapping and collecting of ions that may flow continuouslyinto the TOF pulsing region between acceleration pulses improves theduty cycle efficiency of the TOF, resulting in improved sensitivity.Additional improvements in duty cycle efficiency may be realized whenthe trapping and collection of ions in a pseudo potential well in theTOF pulsing region is coupled to and coordinated with the trapping andrelease of ions in an ion guide external to the TOF pulsing region.Also, the resulting constraints on the spatial and energy distributionsof the collected ion population prior to pulsing into the TOF driftregion improves Time-Of-Flight mass resolving power and mass accuracy.Compression of the spatial and velocity distributions of the ionpopulation by directing the ions to gently collide with a surface orwith inert gas in conjunction with ion trapping and collection resultsin additional improvement to the mass resolving power, mass accuracy,and sensitivity. Ions that are detrimental to the mass analysis, such asMALDI matrix ions of high abundance and low mass that may saturate thedetector, may be eliminated by selection of the range of mass-to-chargevalues that is trapped.

Ions can also be directed to collide with an electrode surface withrelatively high impact energy, resulting in surface-induceddissociation. The fragment ions can be collected and accumulated in thepseudo potential well and may optionally be cooled by collisions withthe surface or inert gas, prior to accelerating the collected ions intothe TOF drift tube for mass analysis. Mass analysis of such fragmentions can improve the mass-to-charge measurement accuracy andquantification performance. Performing SID directly in the TOFacceleration region avoids the loss of fragment ions that inevitablyoccurs when SID is performed external to the TOF acceleration regionfollowed by transport of the fragment ions into the TOF accelerationregion prior to TOF mass analysis. Hence, the present invention improvessensitivity for MS/MS analysis using SID or CID.

In one embodiment of the invention, ions entering the TOF firstaccelerating region are directed toward the bottom of the pseudopotential well by applying a reverse electric field in the TOFacceleration region. Ions collected in the pseudo potential well areaccelerated into the flight tube of a Time-Of-Flight mass analyzer byapplying a forward electric field in the TOF acceleration region. Thecollection of ions in the pseudo potential well and forward accelerationof ion packets can occur at repetition rates exceeding 20 kilohertzallowing TOF pulse repetition rates typically used in atmosphericpressure ion source orthogonal pulsing TOF ion mass-to-charge analysis.

A variety of ion sources can be configured according to the inventionwith the ability to conduct SID with TOF mass analysis. Ions can beproduced directly in the TOF first acceleration region or producedexternal to the first acceleration region. A time-of-flight massspectrometer configured according to the invention can be selectivelyoperated with or without collection of ions in a pseudo potential well,surface induced dissociation, reaction of ions with surfaces, orcollisional cooling by introduction of a collisional cooling gas orcontrolled collisions with a surface, prior to Time-Of-Flight massanalysis. The invention retains the ability to conduct existingionization and TOF analysis techniques. The added ion collection,trapping, and collisional cooling in a pseudo potential well and SIDfragmentation capabilities expands the overall analytical range of aTime-Of-Flight mass analyzer. A Time-Of-Flight mass analyzer configuredand operated according to the invention can be incorporated into ahybrid instrument enhancing MS/MS or MS/MS^(n) operation. Such aninstrument may be configured with a range of atmospheric pressure orvacuum ion sources.

SUMMARY OF THE INVENTION

The pulsing or ion extraction region of a Time-Of-Flight massspectrometer configured with two parallel planar electrodes isconfigured such that neutral, retarding and ion extraction electricfields can be applied between the two electrodes. The electrode farthestfrom the TOF drift region is commonly referred to as the “pusher”electrode of the TOF ion extraction region. In the present invention,the surface of the pusher electrode is configured with a two-dimensionalarray of smaller electrodes, electrically conducting but isolated fromeach other, in a narrow grid pattern spanning at least a portion of thepusher electrode surface. Surfaces composed of an array of electrodes towhich RF voltages are applied have been described by Franzen, in U.S.Pat. No. 5,572,035. The grid array elements can take a variety of forms,including wire tips arranged in a square, hexagonal, etc. array;closely-spaced long parallel wires; a combination of wire tips and awire mesh arranged around the tips; and others. Essentially, when highfrequency potentials are applied to the grid elements in the appropriatemanner, a strongly inhomogeneous high frequency field of low penetrationrange is produced in the space above the electrode surface. This fieldacts phenomenologically as a virtual surface for repelling ions ofeither polarity. The repelling force is referred to as a “pseudo forcefield”, described by a “pseudo potential distribution”, and createseffectively a “pseudo potential barrier” for ions above a certainmass-to-charge value. The concept for describing the action ofhigh-frequency fields on a population of ions in terms of a pseudopotential distribution was originally proposed by Dehmelt, et. al., inAdv. At. Mol. Physics, 3, 53 (1967). Because the pseudo potentialbarrier height decreases with increasing mass, ions with relatively highvalues of mass-to-charge are trapped with reduced efficiency, dependingon the kinetic energy of the ions relative to the amplitude of thehigh-frequency field. Franzen described the use of surfaces, composed ofan array of electrodes with applied RF voltages, in configurations thatallowed their use as ion guides to transport ions. In the presentinvention, RF-field-generating electrode array surfaces are configuredto form at least a portion of the pusher electrode surface of thepulsing region of a TOF mass spectrometer. When a static retardingpotential difference is applied between the parallel planar electrodesof the pulsing region, the combination of this retarding potentialdistribution and the “pseudo potential distribution” near the pusherelectrode creates what may be described phenomenologically as a “pseudopotential well” for charged particles of moderate energy within a widerange of mass-to-charge values near the pusher plate surface.Additionally, other surfaces surrounding the extraction region may beconfigured with any combination of static potential electrodes and/oradditional, independently controllable arrays of electrodes with dynamicelectric fields applied. The surrounding electrode configuration withapplied electric fields create potential or pseudo potential barriers atthe periphery of the extraction region to prevent loss of ions from theextraction region at those boundaries. The electronics providingvoltages to these electrodes is configured such that the neutral,forward and reversed biased (with respect to the TOF axis) staticelectric fields and high frequency fields can be rapidly applied byswitching between power supplies.

In one embodiment of the invention, ions produced in an ion source forman ion beam that enters the pulsing region with the ion beam trajectorysubstantially parallel to the surfaces of the planar electrodes thatdefine the pulsing region. During the time period when ions are enteringthe TOF pulsing region, a slight reverse bias field is applied acrossthe two planar electrodes to direct the ions toward the bottom of thepseudo potential well near the pusher electrode. In this manner ions arecollected and constrained near the pusher electrode, that is, the planarelectrode farthest from the TOF drift region, for a selected period oftime before a forward bias electric field between the planar electrodesis applied, accelerating ions from the pseudo potential well into theTOF tube drift region of the mass analyzer. The primary ion beam may beprevented from entering the pulsing region just prior to applying theion forward accelerating potential to prevent any additional ions fromentering the gap between the electrodes prior to ion acceleration intothe TOF tube. The continuous collection of ions in the pseudo potentialwell near the pusher plate, prior to pulsed acceleration of the ionpopulation into the Time-of-Flight drift tube region, improves the dutycycle by collecting all ions within a wide range of mass-to-charge (m/z)values with equal efficiency prior to pulsing. The duty cycle ofconventional non-trapping continuous beam orthogonal pulsing increasescontinuously with the ion m/z value, discriminating against lower massions. Collecting ions in a pseudo potential well prior to pulsingreduces the m/z duty cycle discrimination in conventional continuous ionbeam orthogonal pulsing Time-Of-Flight mass analysis. The duty cycle isalso improved because the process of collecting ions in the pseudopotential well prior to pulsing, serves as a means of integrating ionsprior to acceleration into the TOF tube. The ion integration orcollection time, however, is limited by space charge buildup in thepseudo potential well, potentially limiting the number of ions which maybe effectively collected prior to pulsing. The space charge build up inthe pseudo potential well can be controlled to some degree by varyingthe pulse repetition rate of ions into the TOF mass analyzer. Pulserates exceeding 20 KHz can be used limited only by the flight time ofthe m/z range of interest. The ability to accumulate only ions within acertain range of m/z values also allows the elimination of ions thatwould otherwise be detrimental to the analysis, such as low-mass, highabundance matrix ions in MALDI.

In another embodiment of the invention, the Time-Of-Flight pulsingregion configured for orthogonal pulsing, comprises two parallel planarelectrodes, between which neutral, retarding and accelerating fields maybe applied, and in which the surface of one electrode, the “pusher”electrode, is configured as an array of separate electrodes which can bepowered to form a pseudo potential barrier near the pusher electrodesurface. The neutral, accelerating, and retarding static electric fieldscan be applied by rapidly switching power supply outputs to one or bothelectrodes. Ions traveling into the pulsing region with trajectoriessubstantially parallel to the planar electrode surfaces, traverse thepulsing region with a neutral electric field applied between the twoplanar electrodes After a selected period of time, a retarding orreverse electric field is applied between the planar electrodesdirecting the ions located in the pulsing region gap toward the pusherelectrode. Depending on the magnitude of the reverse electric field, theions will either be trapped in the pseudo potential well near the pusherelectrode surface, or the ions will collide with the pusher electrodesurface. Again, depending on the magnitude of the reverse electricfield, ions may collide with the pusher electrode surface with enoughenergy to cause surface-induced dissociation and produce fragment ions,or with only enough energy to dissipate some kinetic energy and recoil.In either case, following the collision with the pusher electrodesurface, the surviving ions will be captured in the pseudo potentialwell near the pusher electrode surface. After a preset delay, anaccelerating field is applied between the two planar electrodes and theions are accelerated from the pseudo potential well into theTime-Of-Flight drift region. One or more ion collecting pulses canprecede an extraction pulse into the Time-Of-Flight drift region.

In another embodiment of the invention, the pusher electrode surface,consisting of an array of independent electrodes which are powered tocreate a high-frequency electric field and form a pseudo potentialbarrier near the pusher electrode surface, is coated or manufactured atthe surface with material selected to minimize charge exchange when anion impacts the surface. In some applications, the pusher electrodesurface can be heated to reduce the probability of ions being retainedat the surface upon colliding and/or fragmenting. Surface materials thatminimize charge exchange will improve ion yield in both SID and inenergy-absorbing low impact energy collisions, resulting in higher TOFsensitivity in both cases. In addition to the array of high-frequencyelectrodes that form the pseudo potential barrier near the pusherelectrode surface, the pusher electrode assembly can be comprised ofmultiple electrode segments with different voltages applied to eachsegment. Voltages can be applied to a multiple segment electrode duringion collection to help prevent ions from leaving the pseudo potentialwell in directions normal to the well depth axis, that is, parallel tothe pusher plate surface. Additional electrodes can also be configuredat the periphery of the acceleration region to generate potentials thatconstrain ions in directions normal to the pseudo potential well axis.Such fields can be configured advantageously to reduce the spatialdistribution of ions in these directions normal to the potential wellaxis. This results in a reduction of the effects of field distortions inthe TOF optics, such as from: deflection fields; edge effects, that is,field distortions due to the mechanical design at field boundaries; andgeometrical inaccuracies, such as from mechanical misalignments.

In yet another embodiment of the invention, ions are created in thepulsing region of a Time-Of-Flight mass analyzer while maintaining asubstantially neutral field between the two electrodes of the pulsingregion. The resulting ion population is subsequently directed to apseudo potential well near the pusher electrode, created by theapplication of high-frequency potentials to an array of independentelectrodes in the surface of the pusher electrode, prior to pulsing ofthe ions into the Time-Of-Flight drift region. A specific example ofsuch an embodiment of the invention is the configuration of an ElectronIonization (EI) source in the pulsing region of the Time-Of-Flight massanalyzer. Sample bearing gas is introduced at low pressure into thepulsing region of a Time-Of-Flight mass analyzer with a neutral electricfield applied across the pulsing region gap. An electron-emittingfilament is turned on with the emitted electrons accelerated into thepulsing region gap to ionize the gas phase sample present. Theelectron-emitting filament is turned off and a reverse electric field isapplied across the pulsing region gap to direct the gaseous ionsproduced to move toward a pseudo potential well near the pusherelectrode. When the EI generated ions have been collected in the pseudopotential well near the pusher electrode, an accelerating field isapplied across the pulsing region gap to accelerate the ions into thedrift region of the Time-Of-Flight mass analyzer. The EI generated ionscan initially be directed toward the pseudo potential well near thepusher electrode with sufficient energy to impact the pusher electrodesurface and cause surface induced dissociation, or with low energy toallow non-fragmenting collisions that dissipates ion kinetic energy. Thesample gas may be supplied from a variety of inlet systems including butnot limited to a gas chromatograph. Collecting EI generated ions in apseudo potential well and cooling them by allowing collisions with thepusher surface, or with the introduction of collision gas, prior topulsing into the Time-Of-Flight drift region reduces the ion kineticenergy distribution and spatial spread. This results in higher resolvingpower and mass accuracy Time-Of-Flight mass to charge analysis. Ifelectron ionization occurs in the presence of the pseudo potential welldistribution, the ratio of ionization time to TOF ion acceleration andflight time can be increased resulting in higher overall Time-Of-Flightduty cycle.

In another embodiment of the invention, the pulsing region of aTime-Of-Flight mass analyzer is comprised of two planar electrodespositioned substantially parallel and set a distance apart so as tocreate a gap between them. This gap is referred to as the TOF firstaccelerating or pulsing region. The first electrode positioned furthestfrom the Time-Of-Flight drift region, that is, the “pusher” electrode,is configured as an array of independent electrodes to whichhigh-frequency potentials can be applied so as to create a pseudopotential well near the surface. The second electrode positioned nearestthe TOF drift region is commonly referred to as the “counter” electrode.In conjunction with a static electric field created by static potentialsapplied simultaneously to these two electrodes, as well as possiblyother electrodes bordering the TOF first acceleration region, a pseudopotential well is formed near the pusher electrode, to which ions aredirected prior to pulsing into the Time-Of-Flight drift region. Aneutral, collecting or extraction electric field can be applied betweenthe two pulsing region electrodes to allow collecting of ions in thepseudo potential well near the pusher electrode surface, and to allowthe dissipation of kinetic energy by collisions with the pusher platesurface or with inert gas, prior to pulsing the spatially compressedions into the Time-Of-Flight tube drift region. Alternatively, a laserpulse can be applied to the pusher plate surface to release ions rapidlyinto an accelerating or delayed extraction field. In this embodiment ofthe invention, ions generated external to the TOF pulsing region enterthe pulsing region in a direction substantially not parallel to theplanar electrode surfaces which bound the pulsing region. During thecollection period, a reverse electric field is applied across thepulsing region gap to direct ions to the potential well near the pusherelectrode surface. The ions may enter the pulsing region gap with aninitial trajectory that is directed either toward or away from thepusher electrode surface. After the ion collection period, which mayalso include SID by high-energy collisions with the pusher electrodesurface, or kinetic energy dissipation by low-energy collisions with thepusher electrode surface, or with inert gas, the electric field isreversed in the pulsing region and ions in the pseudo potential wellnear the pusher surface are accelerated into the Time-Of-Flight tube formass to charge analysis. This embodiment of the invention provides ameans for directing ions into a Time-Of-Flight pulsing region from awide variety of ion sources or hybrid instrument electrode geometrieswith minimal impact on the Time-Of-Flight performance. Depending on theelectric field strength applied to direct ions to the pseudo potentialwell, ions can impact the collecting surface with a low impact energy inorder to dissipate ion kinetic energy and avoid surface induceddissociation fragmentation, or with sufficient energy to cause surfaceinduced dissociation fragmentation. Ions can be collected for a periodof time prior to pulsing into the Time-Of-Flight drift region, improvingthe duty cycle for some applications and operating modes.

The invention can be configured with a wide range of ion sourcesincluding but not limited to, Electron Ionization (EI), ChemicalIonization (CI), Laser Desorption (LD), Matrix Assisted Laser Desorption(MALDI), Electrospray (ES), Atmospheric Pressure Chemical Ionization(APCI), Pyrolysis MS, Inductively Coupled Plasma (ICP), Fast AtomBombardment (FAB), and Secondary Ion Mass Spectrometry (SIMS). Ions maybe subjected to one or more mass to charge selection and/orfragmentation steps prior to entering the Time-Of-Flight pulsing region.The Time-Of-Flight mass analyzer may be configured as a single mass tocharge analyzer or as part of a hybrid or tandem instrument. A hybridTime-Of-Flight mass analyzer configured according to the invention, mayinclude multipole ion guides including quadrupole mass analyzers,magnetic sector, ion trap or additional Time-Of-Flight mass analyzers.One version of a hybrid TOF-TOF arrangement was described by V. Martin,et. al. in World Intellectual Property Organization publicationWO077824A1, whereby ions that were mass separated in a firsttime-of-flight drift space are allowed to collide with the finalelectrode of a so-called “reflectron” electrostatic mirror, commonlyemployed in TOF mass spectrometers in order to achieve improved massresolving power. Such collisions produce ion fragmentation, and theresulting fragments are then accelerated in the reflectron and massresolved in the second time-of-flight drift space as they travel towardthe detector.

One embodiment of the present invention would configure the rearelectrode of such a reflectron as an RF-field generating surface whichcreates a local potential barrier near its surface, according to thepresent invention, in addition to a static potential that may be appliedto this electrode to help generate the potential gradient in thereflectron. Additionally, a grid is positioned a short distance in frontof this rear electrode surface, and, in the normal reflectron mode ofoperation, a potential is applied to this grid that corresponds more orless to the potential in the reflectron field at the location of thegrid, so that the field strength is more or less similar on both sidesof the grid, but, in any case, is in the same direction. The potentialgradient in the reflectron, and the potential applied to this grid, areordinarily adjusted so as to allow ion packets of ever increasingmass-to-charge values (mass-to-charge separated during their passagefrom the source to the rear region of the reflectron) to travel pastthis grid as they decelerate; to reverse direction in the region betweenthe grid and the RF-field generating surface; and to re-acceleratethrough the reflectron and into the second drift region toward thedetector. According to the present invention, once a packet of ions of aparticular mass-to-charge value of interest enters the region betweenthe rear electrode RF-field generating surface and the grid just abovethe surface, the potential on this grid is switched to a potential thatresults in an electrostatic field which accelerates the aforementionedions toward the rear RF-field generating surface. Such a potential alsoprevents any additional ions of larger mass-to-charge values from beingable to reach and penetrate the grid, while any ions of lowermass-to-charge values that may have been present would have previouslyexited this region and would have either been accelerated or are beingaccelerated toward the detector. The ions of the selected mass-to-chargevalue are thereby isolated and trapped in a pseudopotential well formedby the combined effect of the pseudopotential barrier created near theRF-field generating surface of the rear reflectron electrode, and thestatic potential gradient created by the potential difference betweenthe grid and the RF-field generating surface, in the same manner asdescribed previously for the TOF pulse acceleration region. According tothe present invention, these trapped ions can be directed to collidewith the RF-field generating surface, either gently in order todissipate their momentum via “collisional cooling” and allow better massresolution in subsequent TOF mass-to-charge analysis; or, the ions maybe directed to collide with the surface with sufficient energy to causefragmentation. Trapped ions can also be fragmented by other well-knownmeans, such as by interaction with a photon beam, electron beam, or ionbeam, etc. The fragment ions may then be “cooled” via subsequentmomentum-dissipating collisions with the surface, and thenmass-to-charge separated in subsequent TOF analysis. A TOF analysis ofthese trapped ions may be performed by applying a fast step change ofthe potential on the rear RF-field generating electrode of thereflectron and/or the potential of the grid above this electrode,thereby creating a pulsed acceleration region in this rear region of thereflectron, which accelerates ions back toward the detector.

A variation of this scheme is to configure the rear electrode of thereflectron, or other similar electrostatic mirror structure, not as asolid surface which supports an RF-field generating electrode structure,but rather as a highly-transparent grid consisting of an array of fine,closely-spaced parallel wires arranged in the plane at the position thatotherwise corresponds to that of the rear electrode of the reflectron.In this grid structure, every other wire is connected together, andconnected to one phase of an RF voltage, and the remaining wires areconnected together and connected to the opposite phase of the RFvoltage. Such a structure generates a highly inhomogeneous RF fieldclose to the plane of the wires and so forms a pseudo potential barriernear the plane of the wires for ions of moderate energy within a widemass range. Ions of a particular mass-to-charge value can be trapped byapplying a repelling potential to an intermediate grid located in frontof the rear RF-field generating grid structure at the proper time, asdescribed above for a solid rear reflectron electrode. After isolatingand trapping ions of a particular mass-to-charge value, the trapped ionscan be fragmented by various means, such as by interactions withphotons, electrons, or ions, any of which can be directed through thetrapping region, or by allowing the trapped ions to collide withsurfaces provided, for example, at the periphery of the trapping region,or by other means. The momenta of the trapped ions and/or ion fragmentscan also be reduced by allowing them to collide with nearby surfaces, orwith gas molecules introduced for this purpose. Trapped ions and/or ionfragments, can then be pulse accelerated along the TOF axis through theRF-field generating wire structure, in the initial TOF direction, bygreatly increasing the DC potential gradient between the intermediatetrapping grid and the RF-field generating wire structure, either with orwithout first removing the RF-field. The ions are pulse accelerated intoa subsequent TOF drift space beyond the first TOF drift space and arethereby mass-to-charge separated. This second TOF mass-to-chargeanalysis can also incorporate additional time-of-flight focusingdevices, such as additional reflectrons, beam blanking devices, etc., inorder to improve TOF performance.

According to the invention, analytical sequences can be run that includeion surface induced dissociation alternating with, or sequential to, gasphase collision induced dissociation in hybrid or tandem mass analyzerconfigurations. The invention can be used to study ion-surfaceinteractions as well with prior mass to charge selected ion populations.The surface of the electrode used for ion collisions, as described inthe invention, may be comprised of a variety of materials including butnot limited to metals or other conductor material, semiconductormaterials, dielectric materials, Self Assembled Monolayers (SAM) orcombinations of materials.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A is diagram of one embodiment of the invention, in which aportion of a planar electrode in the pulsing region of a Time-of-Flightmass spectrometer is configured as an array of electrodes to which RFvoltages are applied to create a pseudo potential barrier for ions abovethis surface.

FIG. 1B is a schematic diagram of a pseudo potential distributioncreated near the RF-field-generating-surface of FIG. 1A, for ions of acertain mass to charge, as a function of the distance from theRF-field-generating surface.

FIG. 1C is a schematic diagram of the pseudo potential well formed forions of a certain mass to charge when the pseudo potential distributionof FIG. 1B is combined with a static retarding potential distribution inthe pulsing region of a Time-Of-Flight mass analyzer.

FIG. 1D is a diagram of an orthogonal pulsing Time-Of-Flight massanalyzer configured with an Electrospray ion source and surfaces in theTime-Of-Flight pulsing region for generating a pseudo potential well inthe Time-Of-Flight pulsing region.

FIGS. 2A through 2D diagram one embodiment of the invention whereininitially trapped ions are introduced batchwise into the Time-Of-Flightpulsing region, collected in the pulsing region pseudo potential welland subsequently accelerated into the Time-Of-Flight tube.

FIGS. 3A through 3D diagram one embodiment of the invention wherein ionsare collected in a pseudo potential well in the Time-Of-Flight pulsingregion from a continuous ion beam prior to acceleration into theTime-Of-Flight tube.

FIG. 4 is a diagram of one embodiment of the invention wherein multiplepower supplies are switched to electrostatic lenses to allow collectionof ions in a pseudo potential well in a TOF pulsing region andacceleration of said ions from the pulsing region of a Time-Of-Flightmass analyzer.

FIG. 5A is a top view diagram of one embodiment of anRF-field-generating surface, consisting of an array of wire tipelectrodes in the plane of the surface, electrically insulated from asurrounding electrode.

FIG. 5B is a top view diagram of one embodiment of anRF-field-generating surface, consisting of an array of parallel wires inthe plane of the surface, electrically insulated from a surroundingelectrode.

FIG. 6 is a side view diagram of a RF-field-generating surface composedof an array of wire tips, electrically separated by a dielectric, withpower supplies, switches and control electronics.

FIGS. 7A through 7D diagram one embodiment of the invention wherein,ions produced by Matrix Assisted Laser Desorption Ionization external tothe pulsing region of a time-of-flight mass analyzer are collected in apseudo potential well near a surface in the pulsing region prior toaccelerating the ions into the flight tube of a Time-Of-Flight massanalyzer.

FIG. 8 is a diagram of one embodiment of the invention wherein ions areproduced from a position above the RF-field-generating surface andpseudo potential well in the pulsing region of a Time-Of-Flight massanalyzer.

FIG. 9 is a diagram of one embodiment of the invention wherein ions areproduce from an initial position behind the RF-field-generating surfaceand pseudo potential well in the pulsing region of a time-of-flight massanalyzer.

FIG. 10 is a diagram of one embodiment of the invention wherein ionsproduced by MALDI ionization are directed through an orifice in theRF-field-generating surface.

FIGS. 11A through 11D diagram one embodiment of the invention whereinions produced by electron ionization in the pulsing region of aTime-Of-Flight mass analyzer are collected in a pseudo potential wellnear a surface prior to acceleration into the flight tube of aTime-Of-Flight mass analyzer.

DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENTS

Time-Of-Flight (TOF) mass analyzers that incorporate a linear or anorthogonal pulsing region as a means for pulsing ion bunches into theTime-Of-Flight tube are well known to those skilled in the art.Orthogonal pulsing Time-Of-Flight (O-TOF) mass analyzers are typicallyconfigured with the ion source located external to the TOF pulsingregion. The primary beam of ions exiting an ion source is directed intothe pulsing region of the TOF with a trajectory oriented substantiallyorthogonal to the axis of the Time-Of-Flight tube drift region. Severaltypes of ion sources can be interfaced with orthogonal pulsingTime-Of-Flight mass analyzers. These include but are not limited toElectron Ionization (EI), Chemical ionization (CI), Photon andMultiphoton Ionization, Fast Atom Bombardment (FAB), Laser Desorption(LD), Matrix Assisted Laser Desorption (MALDI), and Thermospray (TS),sources as well as Atmospheric Pressure Ion (API) sources includingElectrospray (ES), Atmospheric Pressure Chemical Ionization (APCI),Pyrolysis and Inductively Coupled Plasma (ICP) sources. Orthogonalpulsing Time-Of-Flight mass analyzers have been configured in tandem orhybrid mass spectrometers. Ions can be delivered to the Time-Of-Flightorthogonal pulsing region from several mass analyzer types including butnot limited to multipole ion guides including quadrupoles, hexapoles oroctopoles or combinations thereof, triple quadrupoles, magnetic sectormass analyzers, ion traps, Time-Of-Flight, or Fourier transform massanalyzers. Hybrid or tandem instruments allow one or more steps of massto charge selection or mass to charge selection with fragmentation (MSor MS/MS^(n)) combined with orthogonal pulsing Time-Of-Flight massanalysis.

One preferred embodiment of the invention is the configuration of anorthogonal Time-Of-Flight (TOF) pulsing region such that ions enteringthe pulsing region can be directed to a pseudo potential well located inthe pulsing region prior to pulsing the ions into the Time-Of-Flightdrift region, as shown in FIG. 1A. A pseudo potential well is created inthe TOF pulsing region by the combination of a pseudo potential barrierformed near the surface 12 of the planar electrode 11, commonly referredto as the pusher electrode, comprising the boundary of the TOF pulsingregion farthest from the TOF drift region, and a static electric fieldformed in the TOF pulsing region by a potential difference appliedbetween the pusher electrode 11 with surface 12 and the planar electrode13. Planar electrode 13 forms the boundary of the TOF pulsing regionthat is closest to the TOF drift region, commonly referred to as the“counter electrode” or “extraction electrode”. The extraction electrode13 is typically composed of a high-transparency grid, or a plate with anaperture hole or slot so as to allow ions to exit the TOF pulsing regionand proceed into or toward the TOF drift region. The surface 12 ofplanar electrode 11 is composed of an array of electrodes, such as asquare array of wire tips, with neighboring wire tips alternatelyconnected to opposite phases of a high-frequency alternating voltage.The connection of the tips is alternated such that every other tip inboth the horizontal or vertical directions of the grid is the samephase. With the application of a high-frequency alternating voltage tothe electrode array in this manner, a highly inhomogeneoushigh-frequency (RF) alternating electrostatic field is establishedimmediately above the surface 12.

The action of the RF-field that forms above the surface 12 is toalternately attract and repel charged particles. Integrated over time, anet repelling force results. As discussed by Dehmelt, in Adv. At. Mol.Physics, 3, 53 (1967), this integrated repelling force field is oftencalled a “pseudo force field”, described by a “pseudo potentialdistribution”. For a single wire tip, this pseudo potential isproportional to the square of the RF-field strength and decays as afunction of distance r from the tip with a 1/r⁴ dependence.Additionally, the pseudo potential is inversely proportional to both theparticle mass m and the square ω² of the RF frequency ω. For an array ofwire tips, such as described above, the pseudo potential is strongerthan that of a single tip, and decays even more rapidly as a function ofdistance from the surface formed by the tip array. In a distance that islarge compared to the distance between neighboring wire tips, theRF-field is negligible. The net effect is the formation of a steeppseudo potential barrier localized very near the real surface with lowpenetration into the space above the surface for ions of moderatekinetic energies. Similar pseudo potential distributions can be formedabove surfaces that are composed of other array formats, such as thecombination of wire tips and a wire mesh formed around the tips, wherethe tips and the mesh have opposite RF phases applied; and an array ofclosely-spaced long parallel wires, where every other wire has theopposite RF phase applied relative to neighboring wires. The pseudopotential distribution above such surfaces is illustrated in FIG. 1B asa function of distance from the surface. In one embodiment of thepresent invention, such a surface is employed as the pusher electrode inthe pulsed acceleration region of a TOF mass spectrometer Because thepseudo potential distribution penetrates only a very short distanceabove the pusher electrode, the remainder of the pulsed accelerationregion can contain electric fields essentially independent of the localRF-fields above the pusher electrode surface. Therefore, a pulsedacceleration region configured with a pseudo potential distributionabove the pusher electrode surface can utilize all of the methods ofoperating the pulsed acceleration as without the pseudo potentialdistribution near the pusher electrode surface. In particular, afield-free condition can be established everywhere in the pulsedacceleration region away from the RF-fields close to the pusherelectrode surface in order to allow the ions to enter the pulsedacceleration region. Then, a static repelling (“repelling” in the sensethat ions of one polarity are accelerated away from the TOF driftregion) electric field can be established in the acceleration region inaddition to the pseudo potential distribution above the pusher electrodesurface. The combined effect of such a static electric field and that ofthe pseudo potential barrier near the pusher electrode surface is thecreation of a pseudo potential well near the pusher electrode surface.The potential distribution of such a pseudo potential well isillustrated in FIG. 1C. Ions of moderate energies located in the pulsedacceleration region will oscillate indefinitely and therefore be trappedin such a potential well when the strength of the pseudo force fieldabove the pusher electrode surface and the strength of the staticelectric field elsewhere in the acceleration region are large relativeto the kinetic energy of the ions, as measured perpendicular to thepusher electrode surface. The magnitude of these ion oscillations in thepseudopotential well can be minimized if the initial ion beam enteringthe pulsed acceleration region is directed so that the ion beam iscentered near the position of the pseudo potential well minimum when thefields are applied. The beam can be located farther away or closer tothe pusher electrode surface to determine the initial ion energy in theTOF axial direction upon TOF pulsed acceleration.

The present invention allows the performance of the TOF mass analyzer tobe de-coupled from the phase space characteristics of the ion beam inthe pulsed acceleration region. Generally, many performancecharacteristics of the TOF mass analyzer, such as the mass resolvingpower and sensitivity, depend on the initial spatial and velocitydistributions of the ion population, as measured parallel to the TOFaxial direction in the pulsed acceleration region. In general, maximumperformance is achieved when these distributions are minimized. However,the ease with which these distributions can be manipulated andmaintained depends to a large extent on the kinetic energy of the ions.Ion beams with relatively low ion kinetic energies are much moresusceptible to distortion due to ion beam space charge forces, surfacecharge forces, electrostatic focus lens aberrations, fields due tosurface contact potential differences, and other effects. On the otherhand, the effective duty cycle, hence sensitivity, of the TOF massspectrometer declines as the ion energy increases. Therefore, thekinetic energies of ions as they enter the TOF pulsed accelerationregion is typically adjusted to some compromise value, often in thevicinity of 10 eV or more, which frequently results in duty cycles ofonly several percent. In contrast, the present invention allows the TOFperformance to be independent of the phase space characteristics, thatis, the spatial and velocity distributions, of the ions in the initialion beam. Consequently, the initial ion kinetic energies can be reducedto less than ˜1 eV, or even ˜0.5 eV, as they enter the TOF pulsedacceleration region, without loss of performance in terms of massresolution or sensitivity, while resulting in improved TOF duty cycleand hence sensitivity.

Alternatively, ions may be allowed to collide with the pusher electrodesurface if the RF voltage amplitude driving the array of electrodes inthe pusher electrode surface is reduced, and/or if the static retardingelectric field in the pulsed acceleration region is increased. Theenergy by which ions collide with the pusher electrode surface can bevaried by proper adjustment of these voltage amplitudes. Ions can bedirected to the pusher electrode surface with low energy to allowcollisions with little or no fragmentation. Low-energy collisions ofions with the pusher electrode surface prior to acceleration of the ionsinto the Time-Of-Flight drift region serves to decrease the ion energydistribution as kinetic energy is dissipated in the surface during thecollisions. Consequently, the recoiled ions will subsequently oscillatein the pseudo potential well with reduced amplitudes due to theirreduced kinetic energy, and therefore the spatial spread of the ionpopulation will also be reduced. Low energy collisions with the pusherelectrode surface may be more easily facilitated by steering the initialprimary ion beam toward the pusher electrode surface from outside thepulsed acceleration region, or by physically moving the pusher electrodesurface forward toward the primary ion beam axis. Either of theseapproaches also allows the initial ion energy in the TOF axial directionto be adjusted for maximum performance. The reduction in ion kineticenergy and spatial spread result in increased Time-Of-Flight resolvingpower and mass accuracy. Introducing an inert gas with which the ionscan collide during their oscillations in the pseudo potential well canalso dissipate the ions kinetic energy. Alternatively, ions can bedirected to collide with the pusher electrode surface with energysufficient to cause surface induced dissociation (SID) fragmentationwhen the ions impact the surface. The fragment ions can then becollected in the pseudo potential well above the surface prior tosubsequent low-energy surface collisions or collisions with inert gasmolecules to dissipate kinetic energy, subsequent high-energy collisionswith the pusher electrode surface to affect additional SID, or bepulse-accelerated directly into the TOF drift region for mass analysis.Surface induced dissociation can serve as the primary ion fragmentationmethod or can compliment ion fragmentation accomplished with gas phasecollisional induced dissociation conducted in a tandem MS or hybrid massspectrometer prior to performing Time-Of-Flight mass analysis. Oneexample of a hybrid mass analyzer with a preferred embodiment of theinvention is diagrammed in FIG. 1D.

FIG. 1D is a diagram of an orthogonal pulsing Time-Of-Flight massanalyzer configured with an Electrospray (ES) ionization source and amultipole ion guide ion trap. The multipole ion guide that extendscontinuously into multiple vacuum pumping stages can be operated in RFonly, mass to charge selection or ion fragmentation mode as described inU.S. Pat. Nos. 5,652,427; 5,689,111; 5,962,851; and 6,011,259. Theinstrument diagrammed can be operated in MS or MS/MS″ mode with gasphase collisional induced dissociation (CID). In addition, the inventionallows surface induced dissociation and collection of ions in a pseudopotential well prior to pulsing into the flight tube of theTime-Of-Flight mass analyzer. Hybrid Time-Of-Flight mass analyzer 1diagrammed in FIG. 1D includes Electrospray ion source 2, four vacuumpumping stages 3, 4, 5 and 6 respectively, multipole ion guide 8 thatextends into vacuum pumping stages 4 and 5, orthogonal Time-Of-Flightpulsing region 10 including pusher electrode 11 with pusher electrodesurface 12 formed by an array of separate electrodes with applied RFvoltages, Time-Of-Flight drift region 20, single stage ion reflector ormirror 21 and detectors 22 and 23. Liquid sample bearing solution issprayed into Electrospray source 2 through needle 30 with or withoutpneumatic nebulization assist provided by nebulization gas 31. Theresulting ions produced from the Electrospray ionization in Electrospraychamber 33 are directed into capillary entrance orifice 34 of capillary35. The ions are swept though capillary 35 by the expanding neutral gasflow and enter the first vacuum stage 3 through capillary exit orifice36. A portion of the ions exiting capillary 35 continue through skimmerorifice 37 and enter multipole ion guide 8 at entrance end 40 located inthe second vacuum pumping stage 4. Ions exiting ion guide 8 pass throughorifice 43 in exit lens 41 and through orifice 44 of focusing lens 42and are directed into pulsing region or first accelerating region 10 ofTime-Of-Flight mass analyzer 45 with a trajectory that is substantiallyparallel to the surface of planar electrodes 11 and 13. The surfaces ofplanar electrodes 11 and 13 are positioned perpendicular to the axis ofTime-Of-Flight drift tube 20. Pusher electrode surface 12 is configuredas part of pusher electrode 11 and counter or ion extraction electrode13 is configured with a high transparency grid through which ions areaccelerated into Time-Of-Flight drift region 20. Pusher electrodesurface 12 is composed of an array of closely-spaced wire tips arrangedin a two-dimensional grid pattern similar to that of FIG. 5A, whereevery other tip is connected to one phase of a high-frequencyalternating potential, and neighboring tips are connected to theopposite phase of the high-frequency alternating potential. Thehigh-frequency alternating potential may be referenced to a secondvarying or static DC voltage. The tips may be formed in a variety ofways, including the actual termination of wires bundled together butwith each wire electrically isolated from its neighbor wire tips; or byintegrated circuit fabrication methods well known in the integratedcircuit industry; or by microfabrication methods well known to those inthe microfabrication industry. The gap between pusher electrode 11 withpusher surface 12 and counter electrode 13 defines the orthogonalpulsing or first accelerating region 10. The position of pusherelectrode surface 12, with or without the position of pusher electrode11, may be adjusted relative to the primary ion beam centerline, asillustrated in FIGS. 1A and 1D, to bring the ions to a specific locationin the potential well.

During orthogonal pulsing TOF operation, a substantially neutral or zeroelectric field is maintained in pulsing region 10 during the period whenions are entering the pulsing region from multipole ion guide 8. At theappropriate time, an accelerating field is applied between electrodes 11with surface 12 and electrode 13 to accelerate ions into Time-Of-Flighttube drift region 20. During the initial ion acceleration and subsequention flight period, the appropriate voltages are applied to lenses 11,13, 14, steering lenses 15 and 16, flight tube 17, ion reflectorelectrodes 19, post accelerating grid 18 and detector 23 to maximizeTime-Of-Flight resolving power and sensitivity. Ions pulsed from theTime-Of-Flight first accelerating region 10 may be directed to impact ondetector 22 or 23 depending on the analytical result desired. If thepulsed ion beam is steered with steering lenses 15 and 16, detector 22or 23 can be tilted as is described in U.S. Pat. No. 5,654,544 toachieve maximum resolving power, Prior to entering Time-Of-Flightpulsing region 10, the original ion population produced by Electrosprayionizaton may be subjected to one or more mass selection and/orfragmentation steps. Ions may be fragmented through gas phasecollisional induced dissociation (CID) in the capillary skimmer regionby applying the appropriate potentials between the capillary exitelectrode 39 and skimmer 38. In addition, the analytical steps of iontrapping and/or single or multiple step mass to charge selection with orwithout ion CID fragmentation can be-conducted in multipole ion guide 8as described in U.S. Pat. Nos. 5,689,111 and 6,011,259. Said massselection and CID fragmentation steps are achieved by applying theappropriate RF, DC and resonant frequency potentials to rods or poles 7of multipole ion guide 8. A continuous or gated ion beam of theresulting ion population in multipole ion guide 8 can be transmittedinto Time-Of-Flight pulsing region 10 from ion guide 8 through lensorifices 43 and 44 in electrodes 41 and 42, respectively.

FIGS. 2A through 2D illustrate a progression of steps embodied in thepresent invention wherein ions trapped in ion guide 8 are gated intoTime-Of-Flight pulsing region 10 and collected in pseudo potential wellnear surface 12 prior to accelerating said ions into Time-Of-Fright tubedrift region 20. Referring to FIG. 2A, ions 50 are initially trapped inmultipole ion guide 8 by setting a retarding or trapping potential onexit lens 41 relative to the DC offset potential applied to ion guiderods 7 as is described in U.S. Pat. No. 5,689,111. A substantiallyneutral or zero field is initially set in pulsing region 10. Theretarding potential applied to lens 41 is lowered for a set time period,then reapplied, to gate ion packet 51 from ion guide 8 into pulsingregion 10. The translational energy of ion packet 51 is determined bythe voltage difference between the ion guide offset potential and thesubstantially equal voltages initially set on electrodes 11 and 13.During the period when the ions are being gated out of ion guide 8,voltages are applied to electrodes or lenses 41 and 42 to optimize theion transfer into pulsing region 10. Ideally, ions traversing pulsingregion 10 prior to pulsing into TOF tube drift region 20 should have novelocity component in the direction perpendicular to the surface oflenses 11 and 13. As this condition is difficult to achieve,alternatively, the initial ion trajectory in the pulsing region shouldbe directed such that any orthogonal component of velocity should becorrelated to the ion spatial location. Such a condition can beapproximated if ions are directed into the pulsing region as a parallelbeam or from a-point source as is described in U.S. Pat. No. 5,869,829.In practice, ions contained in ion packet 51 that enter Time-Of-Flightpulsing region 10 have the primary direction of their initial velocityparallel to the surface of lenses 11 and 13 with a small component ofvelocity in the non-parallel or orthogonal direction. The lower theaxial velocity component of ion packet 51, the more difficult it is tooptimize the ion trajectory into pulsing region 10. In practice, below10 eV, it becomes difficult to prevent an increase in the orthogonalvelocity and spatial distribution of ion packet 51 as it traversespulsing region 10. In the embodiment of the invention diagrammed in FIG.2, ions traversing pulsing region 10 are directed toward the bottom ofthe pseudo potential well formed by a pseudo potential force field orbarrier near surface 12 of electrode 11 and a static electric fieldformed by a static potential difference between pusher electrodes 11with surface 12 and counter electrode 13, prior to being pulsed intoTime-Of-Flight tube drift region 20. The collection of ions in pseudopotential well near surface 12 prior to extraction, limits any furtherexpansion of the initial ion packet spatial distribution in pulsingregion 10 by the constraining action of the potential and pseudopotential barriers forming the well. Ions can be accumulated over timewithin the pulsed acceleration region, and therefore improvesensitivity, without suffering a loss of mass resolving power due tospatial spreading of the accumulated ion population, at least untilspace charge effects within the well become significant. By directingthe ions to collide with the pusher electrode surface 12 with low-energycollisions, the kinetic energy of the ions can be reduced, leading to asimultaneous reduction in their spatial spread as the lower-energy ionssettle deeper in the pseudo potential well. The accumulation of ionsabove surface 12 allows a lower primary ion beam energy because theparallel quality of the beam need not be as carefully controlled.Consequently, primary ion beam energies even below 1 eV can be directedinto pulsing region 10. The accumulation decouples the initial beamquality from the initial beam pulse. A lower primary ion beam energycauses less ion movement in the pseudo potential well, therebyincreasing trapping efficiency. Generally, the collection of ions in apseudo potential well decouples the TOF pulse from the primary ion beamvelocity or spatial distribution. Consequently, Time-Of-Flight resolvingpower can be improved over a wide range of primary ion beam conditionswith the collection of ions, or of ion fragments resulting from surfaceinduced dissociation, in a pseudo potential well near surface 12 priorto acceleration into Time-Of-Flight tube drift region 20. Examples ofion collection in and extraction sequences from a pseudo potential wellnear surface 12 will be described with reference to FIGS. 2 through 11.

Depending on the initial length of ion packet 51 as determined by thegate ion release time, some Time-Of-Flight mass to charge separation canoccur in the primary ion beam as ion packet 51 traverses pulsing region10. By timing the gate ion release time and the travel time of theresulting ion packet into the pulsing region prior to orthogonalpulsing, a portion of the mass to charge scale can be prevented fromentering Time-Of-Flight tube drift region 20 as described in U.S. Pat.No. 5,689,111. As diagrammed in FIG. 2B, Time-Of-Flight separationoccurs between ions of different mass to charge in initial ion packet 51as ion packet 51 traverses pulsing region 10 forming separate ionpackets 52 and 53. Lower mass to charge ions comprising ion packet 53have a higher velocity than the higher mass to charge ions comprisingion packet 52 causing mass to charge separation as initial ion packet 51traverses pulsing region 10. FIG. 2B shows the point in time where theneutral field in pulsing region 10 has been switched to a field thatdirects the ions in packets 52 and 53 toward electrode 11 andRF-field-generating surface 12. Ions in packet 53 are beyond the usablepulsing region volume and are eliminated from any subsequent extractioninto Time-Of-Flight tube drift region 20. This is desirable in someanalytical applications where lower mass to charge ions that are not ofinterest can deaden detector channels prior to the arrival of highermass to charge ions at the detector surface for a given TOF pulse.Removing lower mass to charge ions in a TOF pulse can increase thesensitivity and reproducibility of higher mass to charge ion detectionfor a given analysis. Elimination of lower mass to charge ions can alsobe achieved with the present invention by adjustment of the amplitude offrequency of the RF-field above the surface 12, which determines thesmallest mass to charge that the field will repel. Ion packet 52 isdirected toward the pseudo potential well minimum near the surface 12,and ions will arrive at the location of the pseudo potential wellminimum with a kinetic energy component normal to surface 12 that isdetermined by the ions' initial kinetic energies in this direction andthe potential difference between the ions' initial positions and theposition of the pseudo potential well minimum. If an ion's kineticenergy is insufficient to surmount the pseudo potential barriersubsequently encountered by an ion near surface 12, then the ion will betrapped in the pseudo potential energy well. If an ion's kinetic energycomponent normal to the surface is sufficient to overcome the pseudopotential barrier near surface 12, then the ion will collide withsurface 12 and either dissipate kinetic energy in the collision uponrecoil, or dissociate into fragment ions due to SID. The surfacecomposition is chosen so as to prevent the retention of ions uponimpact, in these cases. The energy of impact will be determined by thecombination of the parallel and orthogonal kinetic energy components atthe point when the ion impacts the surface. The ion orthogonal velocitycomponent at impact is determined by the strength of the reverseelectric field applied in pulsing region 10, the initial ion position inpulsing region 10 when the reverse electric field is applied, thestrength of the RF-fields experience by the ions as they approach closeto the surface 12, and the initial ion beam kinetic energy.

After applying a collecting or reverse electric field in pulsing region10 for a set time period, the electric field is reversed in pulsingregion 10. FIG. 2C shows the initial position of ion packet 55 comprisedof ions or SID fragment ions located in a pseudo potential well nearsurface 12 just as the forward accelerating electric field is applied,and the RF field may or may not be turned off, in pulsing region 10.Referring to FIG. 2D, the applied forward ion accelerating electricfield accelerates ion packet 56 from near surface 12 and directs theions comprising ion packet 56 into Time-Of-Flight tube drift region 20.The ion trajectory may be altered by applying a non-zero electric fieldbetween steering electrodes 15 and 16. In this manner the ionscomprising extracted ion packet 56 may be directed to impact on detector22 or 23. In one embodiment of the invention, the timing and applicationof voltages to electrodes 41, 42, 11, 13, 15 and 16 are controlled bythe configuration of power supplies, switches and controllers asdiagrammed in FIG. 4.

One embodiment of the invention is shown in FIG. 4 whereRF-field-generating surface 88 is electrically isolated from electrode91 as diagrammed in FIGS. 5A, 5B, and 6. Surface 88 is formed in theembodiment illustrated in FIGS. 5A, 5B, and 6 by wires isolated fromeach other by a dielectric material. In FIGS. 5A and 6, surface 88 isformed by an array of wire tips, where the wires are orientedperpendicular to the surface 88. As illustrated in FIG. 6, neighboringwire tips are alternately connected to opposite phases of ahigh-frequency alternating voltage. The connection of the tips isalternated such that every other tip in both the horizontal or verticaldirections of the grid is the same phase. FIG. 5B illustrates onealternative arrangement of the electrodes forming theRF-field-generating surface 88, in which wires are oriented lengthwisein the plane of the surface 88 and parallel to each other. In thisconfiguration, every other wire is connected to the same phase, andneighboring wires are connected to opposite phases of the RF voltage.The surface of the dielectric material may coincide with the plane ofthe wires, or wire tips as illustrated in FIGS. 6, or, alternatively,the surface of the dielectric may be located either below or above theplane of the wires or wire tips, depending on the most advantageouslocation for supporting surface-collected charge or not, and whether asurface coating of one type or another is employed.

With reference to FIGS. 4, 5A, 5B, and 6, the adjustable RF voltageoutput 402 from RF power supply 400 is connected to theRF-field-generating surface 88. Voltages provided by power supplies 65,66 and 67 are selectively applied to the DC reference input 401 of RFpower supply 400 through switch 61 and therefore the voltages providedby power supplies 65, 66, and 67 define the DC offset potential of RFgenerating surface 88. The outputs of power supplies 65, 66 and 67 areconnected to switch poles 77, 69 and 78, respectively. The voltageapplied to switch output 93 connected to the reference input 401 of RFpower supply 400, is controlled by controller 62 through switch controlline 75. Voltages from power supplies 66 and 67, connected through lines71 and 72 to poles 73 and 80 respectively of switch 70 are selectivelyapplied to electrode 91 through output 98 of switch 70. The voltageapplied to electrode 91 is controlled by switch controller 62 throughcontrol line 76. Switch 60 applies voltages from power supplies 63 and64, connected to poles 68 and 79 respectively, to switch output 92connected to exit lens 41. Switch controller 62 sets the output ofswitch 60 through control line 74 to control the gating or release oftrapped ions from multipole ion guide 8. Voltages from power supplies 81and 82, connected to poles 85 and 84 respectively of switch 83 areapplied to lens 13 through switch 83 output connection 94. The voltageapplied to lens 13 is controlled by switch controller 62 through controlline 86. In the embodiment shown, lens 14 is tied to ground potentialand voltage is applied to lens 42 from power supply 97. Steering lenses15 and 16 are connected to power supplies 95 and 96 respectively. In theembodiment of the invention diagrammed in FIG. 4, the potentials oflenses 42, 14, 15 and 16 remain constant during an ion collecting andextraction cycle as diagrammed in FIG. 2.

Switches 60, 61, 70 and 83 are synchronously controlled by switchcontroller and timer 62. The pole positions of switches 60, 61, 70 and83, as diagrammed in FIG. 4 are set to allow the gating or release oftrapped ions from ion guide 8. The voltages set on power supplies 63,97, 66, and 81 connected to electrodes or lenses 41, 42, 88 with 91 and13 respectively, optimize the initial release of ion packet 51 from ionguide 8 and transfer to pulsing region 10. After the gate ion releasetime period is over, controller 62 switches output 92 of switch 60 topower supply 64 through pole 79 to end the release of ions from ionguide 8. FIG. 2A illustrates the position of released ion packet 51shortly after output 92 of switch 60 has been switched from power supply63 to 64. Variations of trapping and releasing ions from ion guide 8 aredescribed in U.S. Pat. No. 5,689,111 and these alternative means for iontrapping and release can be equally configured in the inventiondescribed herein. After an appropriate delay to allow the desiredportion of ion packet 52 to move into position over surface 88 or 12 asshown in FIG. 2B, controller 62 switches output 93 from power supply 66to 65 through switch 61. This switching of voltages changes thesubstantially neutral or zero electric field in pulsing region 10 to areverse electric field that directs ions toward surface 88. For positiveions, the voltage applied from power supply 65 to surface 88 will beless, or more negative, than the voltage applied to electrodes 91 and13. (While such a reverse electric field is described in this particularembodiment of the present invention as being generated by the reductionin voltage of surface 88 relative to the potentials of electrodes 91 and13, it will be appreciated that an alternative approach is to increasethe potentials of electrodes 91 and 13 relative the DC potential ofsurface 88, which also results in a reverse electric field that directsions towards the surface 88.) Ions may or may not collide with surface88 depending on the amplitude of the relative voltages applied toelectrodes 13, 91 and surface 88, the amplitude of the RF voltageapplied to surface 88, and the initial ion energy in the orthogonaldirection prior to colliding with surface 88. Higher impact energy maybe applied to cause surface induced dissociation or a lower energyimpact may be set to allow energy-dissipating collisions of ions withsurface 88. As shown in FIGS. 4, 5A, 5B, and 6, surface 88 may beconfigured as a subset of the total area of pulsing region electrodeassembly 90.

During the reverse field or collecting step, the output of power supply65 is applied as a bias DC potential directly to collecting surface 88.As diagrammed in FIGS. 4, 5A, 5B and 6, electrode 91 and surface 88 ofelectrode assembly 90 are configured as a planar surface. Surface 88 iselectrically isolated from electrode 91. The voltage applied toelectrode 91 of electrode assembly 90 during the reverse fieldconditions can be set to be substantially equal to the voltage appliedto lens of electrode 13. Alternatively, a voltage different from thatapplied to electrode 13 can be applied to electrode 91 to optimize theion collection or fragmentation conditions during the collection step.Due to the electric field between surface 88 and lens portion 91, ionsare directed substantially toward surface 88 during reverse fieldconditions. The size and position of surface 88 is configured tomaximize the detection efficiency of ions accelerated from surface 88into TOF tube drift region 20.

Referring to FIG. 4, output 93 is switched to power supply 65 togenerate a reverse electric field for a desired time period. Thecollecting time period will vary depending on the field applied inpulsing region 10, the desired time for ions to spend in the pseudopotential well and whether it is desired to collect all ions initiallypositioned in the pulsing region or a portion of the ions prior toaccelerating ions into Time-Of-Flight tube drift region 20. If surface88 is coated with a self assembled monolayer (SAM) material or otherdielectric material, ions allowed to collide with the surface may becometrapped on the surface, and the space charge created by ions initiallycollected on surface 88 may prevent additional ions from colliding withthe surface. Miller et. al., Science, Vol. 275, 1447, 1997, reportedthat an ion soft-landed (that is, with low impact energy) on an F-SAMsurface remains intact without loss of charge for hours when kept undervacuum. The retention of ion charge on the surface can be desirable insome analytical applications. Some degree of space charging maintainedon the surface facilitates the dissipation of energy and subsequentrecoil of ions colliding with the surface under low-energy impactconditions because the space charge prevents the approaching ions fromforming a bond with the surface. The collecting surface can be initiallycharged by conducting one or more initial surface collection cycles.Depending on the surface material used and the initial ions collected onthe surface, such soft-landed ions may not release with the reversal ofthe collecting electric field in pulsing region 10. In this manner aneffective surface space charge steady state can be reached which enablesvery high ion yield from each subsequent low-energy collision. Any smallnon-uniform field created by the space charge which would effecttrajectories of ions traversing pulsing region 10 can be counteracted byapplying the appropriate bias voltage to electrode 13 from power supply81.

A forward accelerating field is applied in pulsing region 10 after thereverse or collecting field has been held for a period of time. Theaccelerating field accelerates ions in the pseudo potential well nearsurface 88 into Time-Of-Flight tube drift region 20. Referring to FIG.4, the rapid application of a forward accelerating field is achieved bysimultaneously switching the output of power supply 67 to collectingsurface 88 and electrode 91 through switches 61 and 70 respectively andthe output of power supply 82 to electrode 13 through switch 83. Theaccelerating field accelerates ions near surface 88 into Time-Of-Flighttube drift region 20. Switch 60 retains its state and the outputs ofpower supplies 97, 95 and 96 remain unchanged. The forward acceleratingfield applied in pulsing region 10, is maintained for a time periodsufficient to allow the highest ion mass-to-charge of interest, to passthrough the grid of ion lens 14 and into Time-Of-Flight tube driftregion 20. After the applied forward acceleration field time period iscomplete, the controller simultaneously switches switch 83 from pole 84to 85, switch 70 from pole 80 to 73, switch 61 from pole 78 to 69 andswitch 60 from pole 79 to 68. This forms a substantially neutral fieldin pulsing region 10 and opens the gate to release ions from ion guide8. This switch event begins a new ion gating, ion collection and TOFforward acceleration cycle. Controller 62, the power supplies andswitches are configured to allow rapid rise time of the voltages appliedto electrodes or lenses 41, 88, 91 and 13. The voltage rise time appliedto electrodes 41, 88, 91 and 13 is generally less than 50 nanoseconds toachieve optimal Time-Of-Flight performance.

Variations to the ion collection and TOF pulsing cycle described can beconfigured by modifying the switching sequence and time delays ascontrolled by controller 62 to optimize performance for a givenanalytical application. For example, it may be desirable to configuremore than one ion gating and collection cycle prior to accelerating ionsinto the time-of-flight drift region. Multiple gating and collectioncycles may serve to accumulate ions in the pseudo potential well nearsurface 88 prior to extraction. Ion collection cycles can be mixed withSID steps prior to ion extraction. In all configurations of theinvention, ions with either positive or negative polarities can bedirected toward surface 88 with the appropriate polarity electric fieldapplied in pulsing region 10. Similarly, the appropriate polarityelectric field can be applied to extract positive or negative ionscollected near surface 88 and accelerate said ions into Time-Of-Flighttube drift region 20. Surfaces 88 can be configured to be automaticallyreplaced without breaking vacuum. With automated exchange from a set ofRF voltage generating surfaces, a given material coating the RFgenerating surface can be rapidly configured to optimize performance fora given application. When the vacuum is vented, a single or a set ofRF-voltage generating surfaces with or without surface coatings can beremoved and reinstalled manually by removal and reinstallation of vacuumflange assembly 49.

Another embodiment of the invention is diagrammed in FIG. 3. Ions from acontinuous beam enter pulsing region 110 from a substantially orthogonaldirection while a reverse electric field is applied between electrode orlens 113 and electrode 111 and RF-generating surface 112. As shown inFIG. 3A, ions comprising continuous primary ion beam 150 enter pulsingregion 110 from multipole ion guide 108 and are directed toward surface112 in the presence of this reverse electric field. Ions are accumulatedin a pseudo potential well near surface 112 for a period of time afterwhich additional ions are prevented from entering pulsing region 110 asdiagrammed in FIG. 3B. Continuous beam 150 can be stopped by applying aretarding or trapping potential to exit lens 141 which prevents ionstraversing multipole ion guide 108 from exiting through exit lens 141.FIG. 3B illustrates the breaking of continuous beam 150 by applying atrapping potential to exit lens 141 and/or a combination of lens 141 and142. The ions in truncated primary ion beam 152 continue into pulsingregion 110 and are directed toward surface 112. When the ions in pulsingregion 110 have been collected in the pseudo potential well near surface112, as represented by ion packet 153 in FIG. 3C, a forward acceleratingelectric field is applied between surface 112 with electrode 111 andelectrode 113, with or without simultaneously shutting off the RF field.The forward accelerating electric field extracts ions in ion packet 153from the pseudo potential well near surface 112 and released ion packet154 is accelerated through the grids of electrodes of lenses 113 and 114into Time-Of-Flight tube drift region 120 as diagrammed in FIG. 3D.Voltages can be applied to steering lenses 115 and 116 to steer thedirection of the ions as ion packet 154 moves into Time-Of-Flight driftregion 120. In the continuous beam embodiment of the invention asdiagrammed in FIG. 3, ions are trapped or accumulated in pseudopotential well near surface 112 with less time spent per cycle trappingions in ion guide 108. High duty cycle can be achieved with thiscontinuous beam embodiment of the invention because few ions are lostthroughout the ion collection in the pseudo potential well andextraction cycle. This is an alternative to the embodiment of theinvention as diagrammed in FIG. 2, wherein more time is spentaccumulating or trapping ions in ion guide 8 prior to collection inpseudo potential well near surface 12. One embodiment or the other mayyield optimal performance depending on the analytical application.

Electrode 145 may be added to pulsing region 110 as shown in FIG. 3 toprovide a retarding potential to the primary ion beam. The kineticenergy, primarily in the axial direction, of ions in primary beam 150 asthey enter pulsing region 110 is set by the voltage difference betweenthe ion guide offset potential and the average field applied toelectrodes 111 and 113 traversed by the primary ion beam. A voltage maybe applied to electrode 145 to reduce the primary ion beam axialvelocity as the ions traverse pulsing region 110. For the dissipation ofion kinetic energy by low-energy collisions with the RF-generatingsurface, it may be desirable to reduce the ion impact energy on thesurface. The ion impact energy on the surface is a function of theprimary beam axial velocity component and the orthogonal component duethe reverse field applied in pulsing region 110. Configuring electrode145 to retard the primary Ion beam axial velocity component allows moreprecise control of the ion impact energy with surface 112. Reducing theprimary ion beam energy as it enters region 110 by lowering thepotential of the ion guide offset relative to that of electrodes 111 and113 is disadvantageous in that this method reduces the ability to shapeand direct the primary ion beam it enters pulsing region 110. Localfringing fields present in the path of the primary ion beam path priorto entering pulsing region 110 have a more pronounced and detrimentaleffect on focusing of the primary ion beam when the ion kinetic energyis reduced below a few tenths of 1 eV. Applying a retarding potential toelectrode 145 during collection of ions on surface 112 allows thesetting of the initial primary beam kinetic energy sufficiently high toachieve efficient transport from ion guide 108 into pulsing region 110.The potential applied to Electrode 145 provides an additional degree ofcontrol of the ion impact energy on surface 112 independent of theprimary ion beam energy as it enters region 110. When a forwardaccelerating potential is applied in pulsing region 110, the appropriatevoltage is applied to electrode 145 to match the field that would appearat its position were it not present. With such a potential appliedduring ion acceleration into TOF tube drift region lens 145 does notdistort the optimal accelerating field established by potentials appliedto electrode 111, surface 112 and electrode 113.

Electrode 145 can also be configured as a surface composed of anRF-field-generating array of electrodes similar to that of surface 112.Therefore, a pseudo potential barrier is formed at the far end of thepulsing region, which prevents loss of ions in this area. Similarly, anRF-field-generating surfaces can be configured on the pulsing regionside of electrode 142 in order to prevent ions trapped in the pseudopotential well near surface 112 from escaping past the area of pulsingregion 110 that is near the electrode 142. Other electrodes may beplaced along other periphery areas bordering the pulsing region with anycombination of static and RF electric fields so as to prevent ionstrapped in pseudo potential well near surface 112 from escaping.Appropriate DC biases can be applied to these additional electrodesduring the TOF acceleration period to minimize distortion of theacceleration field in pulsing region 110 during ion acceleration intothe TOF drift region.

The power supply and voltage-switching embodiment shown in FIG. 4 can beconfigured to control the continuous ion collection and extractionsequence diagrammed in FIG. 3. Replaceable surface 112 and electrode 111can be configured as diagrammed in FIGS. 4, 5A and 5B, and 6, and asdescribed for the embodiment of the invention diagrammed in FIG. 2 and3. In particular, surface space charge formed from ion accumulation on adielectric or a Self Assembled Monolayer surface can be used to preventions from physically contacting the surface during collisions with thesurface prior to acceleration into Time-Of-Flight tube 120. It ispreferable to maintain the magnitude of the surface space charge at areproducibly low level to minimize the effect of the space chargerepelling force on an accelerated ion flight time.

An alternative embodiment of the invention includes an alternative tothe configuration of surface 88 in FIGS. 4, 5A, 5B, and 6. Surface 88may be coated with an appropriate matrix material, as is known in theart, to enable Matrix Assisted Laser Desorption Ionization (MALDI) ofions collected on surface 88. Ions produced from an external ion sourcecan be collected on surface 88 if the interaction between ions collidingwith the surface, as described above, is strong enough so as to retainthe ions on the surface, rather than allowing the ions to recoil withreduced kinetic energy. A laser pulse with the optimal wavelength, powerand duration is directed to impinge on collecting surface 88 to produceMALDI generated ions. The MALDI produced ions can then be acceleratedinto the Time-Of-Flight tube with or without delayed extraction. Thedelay in applying the acceleration pulse relative to the laser pulseallows the Maldi-generated neutral gas plume to dissipate.Alternatively, the MALDI ions produced by one or more laser desorptionpulses can be accumulated in pseudo potential well near surface 88, asdescribed above. The accumulated MALDI produced ions can be directed tocollide with surface 88 with low impact energy so as to dissipatekinetic energy and reduce spatial and velocity distributions in thepseudo potential well, as described previously, prior to pulsedacceleration into the TOF drift region, resulting in improved massresolving power and mass accuracy. The accumulated MALDI ions can alsobe directed to collide with surface 88 with high energy so as to createSID fragment ions, which can subsequently be accelerated into the TOFdrift region, or be accumulated in pseudo potential well above surface88 prior to collisional cooling or acceleration into the TOF driftregion. If the external source is an Electrospray ionization sourceinterfaced on-line to a liquid chromatography (LC) system, ionsgenerated from the ES source are delivered to the collecting surface inthe Time-of-Flight pulsing region. The ions may be soft-landed oraccelerated to the collecting surface with sufficient energy to causesurface induced dissociation fragmentation. The surface collected ionpopulation may or may not be neutralized depending on the MALDI matrixmaterial used. A laser pulse impinging on the collection surfacereleases ions and/or re-ionizes surface neutralized ions prior toacceleration of the product ions into the Time-Of-Flight tube driftregion. Combining surface collection of API source generated ions withsubsequent MALDI of said surface collected ions and surface neutralizedmolecules, allows MALDI mass spectra to be generated on line from LC orcapillary electrophoresis (CE) separations. A Time-Of-Flight massanalyzer can be configured according to the invention whereby ES andMALDI mass spectra can be alternatively generated on-line during anLC-MS or a CE-MS run. MALDI generated ions of higher molecular weightgenerally have fewer charges than ES generated ions from the samecompounds. Depending on the configuration of the collection surfacematerial multiply charged ions produced by ES ionization may have areduction in the number of charges per ion on impact with the collectingsurface. Charge reduction may be desirable in some applications as itspreads ion peaks out along the mass to charge scale, reducing peakdensity.

One aspect of the invention is configuration of heating or cooling ofsurface 88 as diagrammed in FIGS. 5A or 5B. Cooling of surface 88 canaid in the condensing of more volatile ions on the surface prior toMALDI. A reduced surface temperature may also aid in slowing downchemical reactions at the surface or decrease the rate of ion chargeexchange with the surface. Heating surface 88 can aid in the release ofions from the surface when a forward accelerating field is applied.Surface to ion reaction rates may be enhanced by heating the collectingsurface in selected applications. Thermal fragmentation of ions canoccur when ions land on a heated surface. Temperature cycling of thesurface 88 during sample introduction to an API source can add a usefulvariable to surface reaction studies with subsequent Time-OF-Flight massto charge analysis.

An alternative embodiment of the invention is diagrammed in FIGS. 7Athrough 7D. Referring to FIGS. 7A and 7B, ions produced in vacuum froman ion source located outside Time-Of-Flight pulsing region 160 aredirected into pulsing region 160 and collected in pseudo potential wellnear surface 161. As an example of an ion source which produces ions invacuum, FIG. 7 diagrams a Laser Desorption (LD) or Matrix Assisted LaserDesorption Ionization source mounted in the Time-Of-Flight vacuum regionsuch that ions produced from a laser pulse are directed intoTime-Of-Flight pulsing region 160. Removable multiple sample stage 163positions sample 164 in line with laser pulse 167 generated from laser166. In the embodiment shown, sample stage assembly 163 is configuredwhereby the position of sample 164 relative to laser pulse 167 can beadjusted to achieve maximum sample ion yield per laser pulse. Ionsreleased from sample 164 due to an impinging laser pulse, are extractedwith an extraction or accelerating potential applied between samplestage 163 and electrode or lens 165. Alternatively, delayed ionextraction from region 168, between electrode 165 and sample surface164, can be achieved when a neutral field or a weak retarding field isapplied for a period of time during and subsequent to the laser pulsehitting sample surface 164. After the delayed extraction time period,the ion extracting electric field is applied to region 168 betweenelectrode 165 and sample stage 163 to accelerate ions from region 168into pulsing region 160. Whether the ions are extracted from region 164with a constant accelerating field or subsequent to a delayed extractiontime period, the ions are accelerated into Time-Of-Flight pulsing region160 with the ion packet primary velocity component oriented in adirection substantially parallel to the surface of lens or electrode169. In the embodiment diagrammed in FIG. 7B, MALDI generated ions fromsample 164 enter pulsing region 160 with trajectories generallyorthogonal to the axis of Time-Of-Flight drift region 171.

A substantially neutral electric field is maintained in pulsing region160 as the ions produced from laser pulse 167 traverse the pulsingregion. The ions produced from laser pulse 167 and accelerated intopulsing region 160 are diagrammed as ion packets 172 and 173 in FIG. 7B.Ion packet 173 is comprised of the lower mass to charge ions, such asmatrix related ions, created by laser pulse 167 impinging on sample 164.The lower mass to charge ions in ion packet 173 have a higher velocitycomponent after acceleration into region 160 than the higher mass tocharge ions comprising ion packet 172. Ions of different mass to chargeexperience some degree of Time-Of-Flight separation as they traversepulsing region 160. After a selected time period subsequent to laserpulse 167, a reverse electric field is applied in Time-Of-Flight pulsingregion 160 to direct the MALDI generated ions comprising ion packets 172and 173 to move towards pseudo potential well near surface 161 andelectrode 162. The time delay prior to initiating collection can bechosen such that undesired lower mass to charge ions have time to movebeyond pulsing region 160 when the reverse electric field is applied. Asdiagrammed in FIG. 7C, higher mass to charge ions from ion packet 172are collected in pseudo potential well near surface 161 while the lowermass to charge ions form ion packet 173 impact on electrode 162 and arenot collected in pseudo potential well near surface 161. Alternatively,the amplitude and/or the frequency of the RF-field generated abovesurface 161 can be adjusted so as to allow lower mass ions below the“cut-off” mass to charge, as determined by the amplitude and frequencyof the RF-field, to pass through the RF-field and be eliminated from theion population. When the reverse field has been applied for a timeperiod sufficient to collect ions in pseudo potential well near surface161, a forward accelerating electric field is applied in pulsing region160 between electrode 169 and surface 161 and electrode 162. As shown inthe diagram of FIG. 7D, the forward ion accelerating field acceleratesions that are collected in pseudo potential well near collecting surface161 into Time-Of-Flight drift tube region 171.

The voltage switching sequence described for the MALDI ionization step,ion acceleration into pulsing region 160, collection of ions in thepseudo potential well and subsequent acceleration of collected ions intoTime-Of-Flight tube drift region 171, is similar to that described forthe embodiment of the invention described in FIGS. 2 and 4. Individualpower supply outputs can be applied to electrodes or lenses 163, 165,162, surface 161, and 169 through switches synchronized with a switchcontroller with timer. Ions can be accumulated in pseudo potential wellnear surface 161 from one or more MALDI pulses prior to accelerating thecollected ions into Time-Of-Flight drift region 1771. Depending on thesurface material selected for coating of surface 161, surface spacecharge can be used to prevent incoming ions from touching the surfaceduring low-energy collisions, facilitating the dissipation of kineticenergy of the ions through collisions with the surface, and subsequention collection and acceleration into Time-Of-Flight tube drift region171. The coating of removable RF-generating surface 161 can be comprisedof but not limited to conductive, insulating, Self Assembled Monolayer,semiconductor or piezo materials. RF-generating surface holder assembly178 can be configured to allow automatic changing of surface 161 withoutbreaking vacuum. Surface coating materials for surface 161 can beswitched to present the optimal surface for kinetic energydissipation/recoil, fragmentation or accumulation for a givenapplication.

By adjusting the reverse electric field strength in pulsing region 160,MALDI produced ions can be directed to surface 161 with energysufficient to cause surface induced dissociation or with low enoughenergy to result in minimal fragmentation. Controlled SID ionfragmentation can be achieved for MALDI generated ions by selection ofthe relative voltage applied between electrode 169 and electrode 162 andsurface 161. MALDI generated ions moving from region 168 to surface 161will spend sufficient time traversing pulsing region 160 to exhaust fastion fragmentation processes that occur in MALDI ionization. Collectionof MALDI generated ions in a pseudo potential well near surface 161reduces the chemical noise appearing in MALDI TOF mass spectra due tofast ion fragmentation processes that occur in MALDI ionization. Withcollection of MALDI generated ions, ion fragmentation processes will becompleted prior to accelerating the collected ions into Time-Of-Flighttube drift region 171. This results in higher resolving power over awider mass to charge range and easier to interpret mass spectra. AllMALDI produced ions can be collected in a pseudo potential well nearsurface 161, if it is not desirable to eliminate ions in portions of themass to charge scale. Lower mass to charge ions generated from the MALDImatrix may be eliminated using reverse field delayed extractiontechniques in region 168 or with Time-Of-Flight separation in pulsingregion 160 prior to collection as was described above. Analogous to theembodiment diagrammed in FIG. 3, MALDI produced ions can be continuouslycollected by the continuous application of a reverse and a retardingelectric field in pulsing region 160 during the time period when MALDIproduced ions are accelerated from region 168 into pulsing region 160.In this manner, all MALDI produced ions are collected in the pseudopotential well near surface 161 prior to being accelerated intoTime-Of-Flight tube drift region 171.

Any vacuum ion source can be substituted for the Laser Desorption orMALDI ion source diagrammed in FIG. 7 where ions enter pulsing region160 with a trajectory substantially orthogonal to the Time-Of-Flighttube axis. Alternatively, ions produced from atmospheric pressure ionsources or vacuum ion sources can be configured such that the ionsproduced, need not be directed into Time-Of-Flight pulsing region 10,110 or 160 with a trajectory that is substantially orthogonal to theTime-Of-Flight tube axis. Alternative embodiments of the invention arediagrammed in FIGS. 8 and 9 wherein a MALDI ion source is configuredsuch that the sample surface is positioned in front and behind RF-fieldgenerating surfaces 180 and 212 respectively. Referring to FIG. 8, laserpulse 183 from laser 182 is directed onto sample 181 mounted onremovable sample holder 184. Ions produced from laser pulse 182 areaccelerated from region 186 into pulsing region 188 by applying theappropriate voltage, with or without delay extraction, to electrode 185.The MALDI generated ions pass through pulsing region 188 and arecollected on replaceable RF-field generating surface 180. Ions collectedin the pseudo potential well near surface 180 are subsequently extractedfrom the pseudo potential well near surface 180 and accelerated intoTime-Of-Flight tube drift region 191. Analogous to the continuous ionbeam collection sequence diagrammed in FIG. 3, a reverse electric fieldis maintained between electrode 189 and surface 180 and electrode 192 todirect ions accelerated from region 186 toward pseudo potential wellnear surface 180. Ions produced from laser pulse 183 can be immediatelyaccelerated into pulsing region 188 or the ions produced can beaccelerated into pulsing region 188 after a delayed extraction period.Direct acceleration or delayed extraction from region 186 is controlledby the voltage applied to lens 185 relative to the voltage applied toelectrically isolated sample holder 184 during and subsequent to theimpinging of laser pulse 183 on sample 181. Ions collected in pseudopotential well near surface 180 are extracted from the pseudo potentialwell near surface 180 and accelerated through lenses 189 and 190 intoTime-Of-Flight tube drift region 191 by applying a forward acceleratingfield between electrodes 189 and surface 180 and electrode 192 inTime-Of-Flight pulsing region 188. The RF field may or may not be turnedoff during the forward ion acceleration period. Multiple laser pulse andcollecting steps may precede an ion accelerating pulsing intoTime-Of-Flight tube drift region 191.

An alternative ion source mounting configuration is diagrammed in FIG. 9wherein a MALDI ion source is positioned behind RF-field generatingsurface 212. Laser pulse 203 produced from laser 202 impinges on sample200 mounted on removable sample holder 210 releasing ions into region205 above the sample surface. Ions located in region 205 areaccelerated, with or without delayed extraction, into Time-Of-Flightpulsing region 211by applying the appropriate voltages to electrode 201and sample holder 210. A reverse electric field is applied betweenelectrode 207 and RF-field generating surface 212 and electrode 206 inpulsing region 211 to direct ion trajectories toward RF-field generatingsurface 212. Ions directed toward RF-field generating surface 212 willform reversing curved trajectories 204 prior to approaching or impactingon RF-field generating surface 212. In this embodiment of the invention,the relative positions and geometries of ion source 213 andTime-Of-Flight pulsing region 211 with RF-field generating surface 212can be configured in a manner that a spatial dispersion of ions canoccur across the plane of RF-field generating surface 212 based on theinitial ion energy and trajectory. This ion surface position dispersioncan be used to selectively eliminate a portion or portions of theinitially produced ion population from being captured in the pseudopotential well above surface 212, and therefore prevented from beingsubsequently accelerated into Time-Of-Flight tube drift region 208.Depending on the size of the region of surface 212 that generates the RFfield above it, ions of only a selected initial ion energy andtrajectory will be trapped prior to acceleration into Time-Of-Flighttube drift region 208. Initial ion energy can be selected by setting theappropriate electric fields in regions 205 and 211 during the pseudopotential well trapping period.

As diagrammed in FIG. 10, sample surface 216 can alternatively bepositioned behind but parallel with RF-generating surface 215.RF-generating surface 215 configured with an orifice positioned oversample 216 serves as the ion extracting electrode. In the embodimentdiagrammed in FIG. 10 the laser is configured to direct laser pulse 217up the TOF tube to impinge sample 216, producing MALDI generated ions.MALDI generated ions entering pulsing region 219 through orifice 214 inRF-generating surface 215 are reflected back toward RF-generatingsurface 215 by applying a reverse electric field in pulsing region 219.Ions collected in pseudo potential well above surface 215 aresubsequently accelerated into the Time-Of-Flight tube drift region byapplying an accelerating field in pulsing region 219.

Another embodiment of the invention, as diagrammed in FIGS. 11A through11D, is the configuration of a vacuum ion source that generates ions byElectron Ionization (EI) in Time Of-Flight pulsing region 231 withsubsequent collection of the produced ions in a pseudo potential wellabove surface 220. Ions collected in pseudo potential well near surface220 are then pulsed into Time-Of-Flight tube drift region 230 where theyare mass to charge analyzed. Referring to FIG. 11A, sample-bearing gas229 is introduced into Time-Of-Flight pulsing region 231 through gasinlet tube 223. The neutral gas may be the output of a gaschromatography column that is introduced into the vacuum maintained inpulsing region 231. Pulsing region 231 and Time-Of-Flight tube driftregion may be configured in different vacuum pumping stages in thisembodiment of the invention to maintain the required vacuum pressures inTime-Of-Flight tube drift region 230 while allowing gas pressuresgreater than 1×10⁻⁵ torr in pulsing region 231. The pressure in pulsingregion 231 can be decreased by configuring a pulsed gas inlet valve withgas pulsing synchronized with electron bombardment ionization,collection in a pseudo potential well above surface 220, andTime-Of-Flight pulsing cycles. A continuous neutral gas source can beused if the pressure in pulsing region 231 is maintained sufficientlylow to avoid ion to neutral collisions during ion acceleration from thepseudo potential well near surface 220 into Time-Of-Flight tube driftregion 230.

Sample bearing neutral gas from a continuous or pulsed gas sourceintroduced into pulsing region 231 is ionized by electron beam 225,generated from filament and repeller assembly 224. Electron beam 225 isaccelerated into pulsing region 231 when the electric field betweenelectrode 227 and surface 220 and electrode 221 is maintainedsubstantially neutral. After a selected ionization time period, electronbeam 225 is turned off and ions 226 formed in pulsing region 231 aredirected toward RF-generating surface 220 by applying a reverse electricfield between electrode 227 and RF-generating surface 220 and electrode221. A pulsed gas source may be closed during the period that ions arecollected in pseudo potential well above surface 220. FIG. 11B diagramsthe acceleration of ions 226 towards surface 220 when a reverse electricfield is applied in pulsing region 231. Ions can be accelerated towardsurface 220 with energy sufficient to cause the ions by pass through thepseudo potential well and collide with the surface 220, causing surfaceinduced dissociation, by applying the appropriate reverse electric fieldin pulsing region 231. Alternatively, ions can be directed to collidewith surface 220 with low energy impact with lower reverse fieldsapplied for dissipating kinetic energy of the ions. Analogous to theapparatus and ion collecting methods described for FIGS. 2, 3, 4, 5 and6, RF-generating surfaces may be coated with materials comprised of butnot limited to conductive, dielectric, semiconductor, multilayer, SelfAssembled Monolayer or piezo electric materials. The RF-generatingsurface mounted to vacuum flange 233 is removable and can be configuredas part of assembly 90 as diagrammed in FIGS. 5A and 5B. The voltagesapplied to electrodes 221, 227 and 228 and RF-generating surface 220 canbe controlled by a power supply and switch configuration similar to thatdiagrammed in FIG. 4. The controller and timer may also be configured toswitch the gas inlet pulsing valve that controls the flow of gas throughgas inlet 223. When the EI source configured in FIG. 11 is operated suchthat a space charge occurs on RF-generating surface 220, ions cancollide with RF-generating surface 220 without being retained on surface220. This method of operation facilitates the dissipation of kineticenergy of the ions prior to being trapped in pseudo potential nearsurface 220 before the ion accelerating field is applied in pulsingregion 231.

When operating with a gas pulsing valve, ions 232 can be held in thepseudo potential well near the RF-generating surface for a period oftime to allow a portion of the residual neutral gas in pulsing region231 to pump away after the ion collection step. This increases the meanfree path and minimizes ion to neutral collisions when the ions areaccelerated from surface 220 into the Time-Of-Flight tube drift regionfor mass to charge analysis. However, this delay also allows collisionsbetween the ions in pseudo potential well and the remaining gasmolecules. Such collisions are an effective way to dissipate kineticenergy of the ions, leading to reduction of their spatial and velocitydistributions, and resulting in better mass resolving power andmass-to-charge measurement accuracy. FIG. 11C diagrams the point in timejust prior to applying the forward accelerating field in pulsing region231. Neutral gas pressure 229 has been reduced during the collectiontime period. As diagrammed in FIG. 11D, a forward electric field isapplied in pulsing region 231 accelerating ions from the pseudopotential well near surface 220 through the grids of electrodes 227 and228 into Time-Of-Flight drift region 230. The RF-field may or may not beturned off during the ion TOF pulse acceleration period. Subsequently, aneutral field is reapplied in pulsing region 231 and sample bearing gasis reintroduced into pulsing region 231 and ionized by ElectronIonization. The embodiment of the invention, as diagrammed in FIG. 11,improves Time-Of-Flight mass analysis resolving power and mass-to-chargemeasurement accuracy when operating with an EI source. Ions created witha large spatial and energy spread in pulsing region 231, are collectedin the pseudo potential well near surface 220, constraining the spatialand energy spread prior to ion acceleration into Time-Of-Flight tubedrift region 230. Collisional cooling of the trapped ions either fromcollisions of the ions with the surface or with residual gas moleculesresults in further reduction of the ions' spatial and energy spread, andimprovement of the mass resolving power and mass-to-charge measurementaccuracy.

A wide range of ion sources can be configured with the inventionsdescribed herein. Multiple ion sources can be configured in a TOF orhybrid TOF mass analyzer. For example, an EI source, orthogonal pulsingAPI source, and a MALDI source can be configured simultaneously in oneTOF mass analyzer according to the invention. EI or Chemical ionizationsources can be configured external the TOF pulsing region. Theinventions can also be configured with a range of time-of-flightanalyzer configurations that include ion reflectors, steering lenses andmultiple detectors. A variety of vacuum system arrangements can beconfigured with the inventions as well. It is clear to one skilled inthe art that variations in time-of-flight mass analyzers, controlsystems, RF-generating surface materials, RF electrode configurationsfor generating RF-fields above surfaces, pulsing region geometries, ionsources and hybrid mass analyzers can be configured that fall within thescope of the invention. The invention can also be configured with othermass analyzer types such as Fourier Transform mass spectrometer (FTMS)and three dimensional quadrupole ion trap mass spectrometers. Theinvention can be configured to reduce the ion energy spread of an ionpacket or to cause SID fragmentation of ions prior to transferring theions into the FTMS cell or an ion trap. Higher ion trapping efficiencycan be achieved in FTMS and ion trap mass analyzers when the energy andspatial spread of the primary ion beam is reduced by collection of ionsand collisional cooling in a pseudo potential well near a surface. SIDfragmentation allows higher fragmentation energy than can be achieved ingas phase CID in either the FTMS cell or ion trap mass analyzer.Combining a SID with FTMS and ion trap mass analyzers extends theirrange analytical capability. In hybrid mass analyzer configurationssingle or multiple steps of ion mass to charge selection, ionfragmentation or ion mobility separation can be conducted prior todirecting the resulting ion population to the pseudo potential well neara surface in the pulsing region of a mass analyzer.

Having described this invention with regard to specific embodiments, itis to be understood that the description is not meant as a limitationsince further modifications and variations may be apparent or maysuggest themselves to those skilled in the art. It is intended that thepresent application cover all such modifications and variations as fallwithin the scope of the appended claims.

What is claimed:
 1. An apparatus for trapping ions, comprising: (a) anarray of electrodes; (b) applying AC voltages of different phases toadjacent electrodes of said array of electrodes; (c) at least one DCoffset voltage applied to said electrodes of said array of electrodes;(d) a counter electrode; (e) at least one DC voltage applied to saidcounter electrode; and (f) means to control said AC and DC voltages totrap ions in a region between said array of electrodes and said counterelectrode.
 2. An apparatus according to claim 1 wherein said AC voltageshave substantially opposite relative phases.
 3. An apparatus accordingto claim 1 wherein the frequency of said AC voltages is radio frequency.4. An apparatus according to claim 1 wherein said electrode array isformed by electrodes comprising metal wire tips.
 5. An apparatusaccording to claim 1 wherein said electrode array is formed byelectrodes comprising metal wires.
 6. An apparatus according to claim 1wherein said alternating electrodes comprise a metal mesh and isolatedmetal wire tips within cells formed by said mesh.
 7. An apparatusaccording to claim 1 further comprising means to produce fragment ionsfrom said ions by surface induced dissociation on a surface within saidtrapping region.
 8. An apparatus according to claim 1 further comprisingmeans to collide said ions on a surface within said trapping regionwithout fragmentation.
 9. An apparatus according to claim 1 furthercomprising a coating over said array of electrodes.
 10. An apparatusaccording to claim 9 further comprising means to produce fragment ionsfrom said ions by surface induced dissociation on said coating.
 11. Anapparatus according to claim 9 further comprising means to collide saidions on said coating without fragmentation of said ions.
 12. Anapparatus according to claim 9 wherein said coating comprises aconductive material.
 13. An apparatus according to claim 9 wherein saidcoating comprises a dielectric material.
 14. An apparatus according toclaim 9 wherein said coating comprises a self-assembled monolayermaterial.
 15. An apparatus according to claim 9 wherein said coatingcomprises a MALDI matrix material.
 16. The apparatus according to claim15 wherein said ions are retained at the surface of said coating, andsaid surface collected ions or molecules formed from surface neutralizedions are extracted from said surface using a MALDI laser pulse.
 17. Anapparatus according to claim 9 wherein said coating comprises apiezoelectric material.
 18. An apparatus according to claim 9 whereinsaid coating comprises a semiconductive material.
 19. An apparatusaccording to claim 1 further comprising an ion source that generatesions from a sample substance located apart from said trap region andmeans for directing said ions into said trap region.
 20. An apparatusaccording to claim 18 wherein said ion source is an atmospheric pressureion source.
 21. An apparatus according to claim 18 wherein said ionsource is an Electrospray ion source.
 22. An apparatus according toclaim 18 wherein said ion source is an Atmospheric Pressure ChemicalIonization ion source.
 23. An apparatus according to claim 18 whereinsaid ion source is a Matrix Assisted Laser Desorption Ionization ionsource.
 24. An apparatus according to claim 18 wherein said ion sourceproduces ions in vacuum.
 25. An apparatus according to claim 18 whereinsaid ion source is an Electron Impact Ionization ion source.
 26. Anapparatus according to claim 18 wherein said ion source is a ChemicalIonization ion source.
 27. An apparatus according to claim 18 furthercomprising means for conducting mass-to-charge selection of ions priorto directing said mass-to-charge selected ions into said trap region.28. An apparatus according to claim 18 further comprising means forconducting fragmentation of said ions prior to directing said fragmentions into said trap region.
 29. An apparatus according to claim 28wherein said fragmentation occurs due to gas phase collisional induceddissociation in a multipole ion guide.
 30. An apparatus according toclaim 28 wherein mass-to-charge selection is conducted prior to saidfragmentation.
 31. An apparatus according to claim 19 further comprisingmeans for conducting mass-to-charge selection and fragmentation of saidions prior to directing said mass-to-charge selected and fragment ionsinto said trap region.
 32. An apparatus according to claim 19 furthercomprising means for trapping and releasing of said ions between saidion source and said trap region.
 33. An apparatus according to claim 19further comprising means for conducting mass-to-charge selection andfragmention of ions prior to directing said mass-to-charge selected andfragmented ions into said trap region.
 34. An apparatus according toclaim 1 wherein ions are created from sample substance molecules byionization means within said trap region.
 35. An apparatus according toclaim 34 wherein said ionization means comprise electrons.
 36. Anapparatus according to claim 34 wherein said ionization means comprisephotons.
 37. An apparatus according to claim 34 wherein said ionizationmeans comprise ions.
 38. An apparatus according to claim 1 wherein saidarray of electrodes is heated to a temperature above ambienttemperature.
 39. An apparatus according to claim 1 wherein said array ofelectrodes is cooled to a temperature below ambient temperature.
 40. Anapparatus according to claim 1 wherein said array of electrodes isreplaceable.
 41. An apparatus according to claim 1 further comprisingmeans to provide neutral gas molecules within said trap region forcollisional cooling of said ions.
 42. An apparatus for analyzingchemical species, comprising: (a) an array of electrodes; (b) applyingAC voltages of different phases to adjacent electrodes of said array ofelectrodes; (c) at least one DC offset voltage applied to saidelectrodes of said array of electrodes; (d) a counter electrode; (e) atleast one DC voltage applied to said counter electrode; and (f) means tocontrol said AC and DC voltages to trap ions in a region between saidarray of electrodes and said counter electrode; (g) a mass analyzer; and(h) means for transferring said ions from said trap region to said massanalyzer.
 43. An apparatus according to claim 42 wherein said ACvoltages have substantially opposite relative phases.
 44. An apparatusaccording to claim 42 wherein the frequency of said AC voltages is radiofrequency.
 45. An apparatus according to claim 42 wherein said electrodearray is formed by electrodes comprising metal wire tips.
 46. Anapparatus according to claim 42 wherein the electrode array is formed byelectrodes comprising metal wires.
 47. An apparatus according to claim42 wherein said alternating electrodes comprise a metal mesh andisolated metal wire tips within cells formed by said mesh.
 48. Anapparatus according to claim 42 further comprising means to producefragment ions from said ions by surface induced dissociation on asurface within said trapping region.
 49. An apparatus according to claim42 further comprising means to collide said ions on a surface withinsaid trapping region without fragmentation.
 50. An apparatus accordingto claim 42 further comprising a coating over said array of electrodes.51. An apparatus according to claim 50 further comprising means toproduce fragment ions from said ions by surface induced dissociation onsaid coating.
 52. An apparatus according to claim 50 further comprisingmeans to collide said ions on said coating without fragmentation of saidions.
 53. An apparatus according to claim 50 wherein said coatingcomprises a conductive material.
 54. An apparatus according to claim 50wherein said coating comprises a dielectric material.
 55. An apparatusaccording to claim 50 wherein said coating comprises a self-assembledmonolayer material.
 56. An apparatus according to claim 50 wherein saidcoating comprises a MALDI matrix material.
 57. The apparatus accordingto claim 56 wherein said ions are retained at the surface of saidcoating, and said surface collected ions or moecules formed from surfaceneutralized ions are extracted from said surface using a MALDI laserpulse.
 58. An apparatus according to claim 50 wherein said coatingcomprises a piezoelectric material.
 59. An apparatus according to claim50 wherein said coating comprises a semiconductive material.
 60. Anapparatus according to claim 42 further comprising an ion source thatgenerates ions from a sample substance located apart from said trapregion and means for directing ions into said trap region.
 61. Anapparatus according to claim 60 wherein said ion source is anatmospheric pressure ion source.
 62. An apparatus according to claim 60wherein said ion source is an Electrospray ion source.
 63. An apparatusaccording to claim 60 wherein said ion source is an Atmospheric PressureChemical Ionization ion source.
 64. An apparatus according to claim 60wherein said ion source is a Matrix Assisted Laser Desorption Ionizationion source.
 65. An apparatus according to claim 60 wherein said ionsource produces ions in vacuum.
 66. An apparatus according to claim 60wherein said ion source is an Electron Impact Ionization ion source. 67.An apparatus according to claim 60 wherein said ion source is a ChemicalIonization ion source.
 68. An apparatus according to claim 60 furthercomprising means for conducting mass-to-charge selection of ions priorto directing said mass-to-charge selected ions into said trap region.69. An apparatus according to claim 60 further comprising means forconducting fragmentation of said ions prior to directing said fragmentions into said trap region.
 70. An apparatus according to claim 69wherein said fragmentation occurs due to gas phase collisional induceddissociation in a multipole ion guide.
 71. An apparatus according toclaim 69 wherein mass-to-charge selection is conducted prior to saidfragmentation.
 72. An apparatus according to claim 60 further comprisingmeans for conducting mass-to-charge selection and fragmentation of saidions prior to directing said mass-to-charge selected and fragment ionsinto said trap region.
 73. An apparatus according to claim 60 furthercomprising means for trapping and releasing of said ions between sourceand said trap region.
 74. An apparatus according to claim 60 furthercomprising means for conducting mass-to-charge selection and fragmentionof ions prior to directing said mass-to-charge selected and fragmentedions into said trap region.
 75. An apparatus according to claim 42wherein ions are created from sample substance molecules by ionizationmeans within said trap region.
 76. An apparatus according to claim 75wherein said ionization means comprise electrons.
 77. An apparatusaccording to claim 75 wherein said ionization means comprise photons.78. An apparatus according to claim 75 wherein said ionization meanscomprise ions.
 79. An apparatus according to claim 42 wherein said arrayof electrodes is heated to a temperature above ambient temperature. 80.An apparatus according to claim 42 wherein said array of electrodes iscooled to a temperature below ambient temperature.
 81. An apparatusaccording to claim 42 wherein said array of electrodes is replaceable.82. An apparatus according to claim 42 further comprising means toprovide neutral gas molecules within said trap region for collisionalcooling of said ions.
 83. An apparatus according to claim 42 whereinsaid mass spectrometer comprises a Time-of-Flight Mass Spectrometer. 84.An apparatus according to claim 42 wherein said mass spectrometercomprises a Time-of-Flight Mass Spectrometer with an ion reflector. 85.An apparatus according to claim 42 wherein said mass spectrometercomprises a Fourier Transform Mass Spectrometer.
 86. An apparatusaccording to claim 42 wherein said mass spectrometer comprises aQuadrupole Mass Filter.
 87. An apparatus according to claim 42 whereinsaid mass spectrometer comprises a Three-dimensional Quadrupole Ion TrapMass Spectrometer.
 88. An apparatus according to claim 42 wherein saidmass spectrometer comprises a Two-dimensional Quadrupole Ion Trap MassSpectrometer.
 89. An apparatus according to claim 42 wherein said meansfor transferring said ions from said trap region to said mass analyzerfor mass-to-charge analysis comprises an electric field applied in saidtrap region.
 90. An apparatus for analyzing chemical species comprisinga Time-of-Flight mass analyzer comprising a pulsing region and adetector, said pulsing region comprising: (a) an array of electrodes;(b) applying AC voltages of different phases to adjacent electrodes ofsaid array of electrodes; (c) at least one DC offset voltage applied tosaid electrodes of said array of electrodes; (d) a counter electrode;(e) at least one DC voltage applied to said counter electrode; (f) meansto control said AC and DC voltages to trap ions in a region between saidarray of electrodes and said counter electrode; and (g) means to controlsaid AC and DC voltages to pulse ions out of said trap region forTime-of-Flight mass analysis.
 91. An apparatus according to claim 90wherein said AC voltages have substantially opposite relative phases.92. An apparatus according to claim 90 wherein the frequency of said ACvoltages is radio frequency.
 93. An apparatus according to claim 90wherein said electrode array is formed by electrodes comprising metalwire tips.
 94. An apparatus according to claim 90 wherein the electrodearray is formed by electrodes comprising metal wires.
 95. An apparatusaccording to claim 90 wherein said alternating electrodes comprise ametal mesh and isolated metal wire tips within cells formed by saidmesh.
 96. An apparatus according to claim 90 further comprising means toproduce fragment ions from said ions by surface induced dissociation ona surface within said trapping region.
 97. An apparatus according toclaim 90 further comprising means to collide said ions on a surfacewithin said trapping region without fragmentation.
 98. An apparatusaccording to claim 90 further comprising a coating over said array ofelectrodes.
 99. An apparatus according to claim 98 further comprisingmeans to produce fragment ions from said ions by surface induceddissociation on said coating.
 100. An apparatus according to claim 98further comprising means to collide said ions on said coating withoutfragmentation of said ions.
 101. An apparatus according to claim 98wherein said coating comprises a conductive material.
 102. An apparatusaccording to claim 98 wherein said coating comprises a dielectricmaterial.
 103. An apparatus according to claim 98 wherein said coatingcomprises a self-assembled monolayer material.
 104. An apparatusaccording to claim 98 wherein said coating comprises a MALDI matrixmaterial.
 105. The apparatus according to claim 104 wherein said ionsare retained at the surface of said coating, and said surface collectedions or molecules formed from surface neutralized ions are extractedfrom said surface using a MALDI laser pulse.
 106. An apparatus accordingto claim 98 wherein said coating comprises a piezoelectric material.107. An apparatus according to claim 98 wherein said coating comprises asemiconductive material.
 108. An apparatus according to claim 90 furthercomprising an ion source that generates ions from a sample substancelocated apart from said pulsing region, and means for directing saidions into said pulsing region.
 109. An apparatus according to claim 108wherein said ion source is an atmospheric pressure ion source.
 110. Anapparatus according to claim 108 wherein said ion source is anElectrospray ion source.
 111. An apparatus according to claim 108wherein said ion source is an Atmospheric Pressure Chemical Ionizationion source.
 112. An apparatus according to claim 108 wherein said ionsource is a Matrix Assisted Laser Desorption Ionization ion source. 113.An apparatus according to claim 108 wherein said ion source producesions in vacuum.
 114. An apparatus according to claim 108 wherein saidion source is an Electron Impact Ionization ion source.
 115. Anapparatus according to claim 108 wherein said ion source is a ChemicalIonization ion source.
 116. An apparatus according to claim 108 furthercomprising means for conducting mass-to-charge selection of ions priorto directing said mass-to-charge selected ions into said pulsing region.117. An apparatus according to claim 108 further comprising means forconducting fragmentation of said ions prior to directing said fragmentions into said pulsing region.
 118. An apparatus according to claim 117wherein said fragmentation occurs due to gas phase collisional induceddissociation in a multipole ion guide.
 119. An apparatus according toclaim 117 wherein mass-to-charge selection is conducted prior to saidfragmentation.
 120. An apparatus according to claim 108 furthercomprising means for conducting mass-to-charge selection andfragmentation of said ions prior to directing said mass-to-chargeselected and fragment ions into said pulsing region.
 121. An apparatusaccording to claim 108 further comprising means for trapping andreleasing of said ions between said ion source and said pulsing region.122. An apparatus according to claim 108 further comprising means forconducting mass-to-charge selection and fragmentation of ions prior todirecting said mass-to-charge selected and fragmented ions into saidpulsing region.
 123. An apparatus according to claim 90 wherein ions arecreated from sample substance molecules by ionization means within saidpulsing region.
 124. An apparatus according to claim 123 wherein saidionization means comprise electrons.
 125. An apparatus according toclaim 123 wherein said ionization means comprise photons.
 126. Anapparatus according to claim 123 wherein said ionization means compriseions.
 127. An apparatus according to claim 90 wherein said array ofelectrodes is heated to a temperature above ambient temperature.
 128. Anapparatus according to claim 90 wherein said array of electrodes iscooled to a temperature below ambient temperature.
 129. An apparatusaccording to claim 90 wherein said array of electrodes is replaceable.130. An apparatus according to claim 90 further comprising means toprovide neutral gas molecules within said pulsing region for collisionalcooling of said ions.
 131. An apparatus according to claim 90 whereinsaid Time-of-Flight Mass Spectrometer comprises an ion reflector. 132.An apparatus for analyzing chemical species comprising a Time-of-Flightmass analyzer comprising an ion reflector, said ion reflectorcomprising: (a) an array of electrodes; (b) applying AC voltages ofdifferent phases to adjacent electrodes of said array of electrodes; (c)at least one DC offset voltage applied to said electrodes of said arrayof electrodes; (d) a counter electrode; (e) at least one DC voltageapplied to said counter electrode; (f) means to control said AC and DCvoltages to trap ions in a region between said array of electrodes andsaid counter electrode; and (g) means to control said AC and DC voltagesto pulse ions out of said trap region for Time-of-Flight mass analysis.133. An apparatus according to claim 132 wherein said AC voltages havesubstantially opposite relative phases.
 134. An apparatus according toclaim 132 wherein the frequency of said AC voltages is radio frequency.135. An apparatus according to claim 132 wherein said electrode array isformed by electrodes comprising metal wire tips.
 136. An apparatusaccording to claim 132 wherein the electrode array is formed byelectrodes comprising metal wires.
 137. An apparatus according to claim132 wherein said alternating electrodes comprise a metal mesh andisolated metal wire tips within cells formed by said mesh.
 138. Anapparatus according to claim 132 further comprising means to producefragment ions from said ions by surface induced dissociation on asurface within said trapping region.
 139. An apparatus according toclaim 132 further comprising means to collide said ions on a surfacewithin said trapping region without fragmentation.
 140. An apparatusaccording to claim 132 further comprising a coating over said array ofelectrodes.
 141. An apparatus according to claim 140 further comprisingmeans to produce fragment ions from said ions by surface induceddissociation on said coating.
 142. An apparatus according to claim 140further comprising means to collide said ions on said coating withoutfragmentation of said ions.
 143. An apparatus according to claim 140wherein said coating comprises a conductive material.
 144. An apparatusaccording to claim 140 wherein said coating comprises a dielectricmaterial.
 145. An apparatus according to claim 140 wherein said coatingcomprises a self-assembled monolayer material.
 146. An apparatusaccording to claim 140 wherein said coating comprises a MALDI matrixmaterial.
 147. The apparatus according to claim 146 wherein said ionsare retained at the surface of said coating, and said surface collectedions or molecules formed from surface neutralized ions are extractedfrom said surface using a MALDI laser pulse.
 148. An apparatus accordingto claim 140 wherein said coating comprises a piezoelectric material.149. An apparatus according to claim 140 wherein said coating comprisesa semiconductive material.
 150. An apparatus according to claim 132wherein said array of electrodes is heated to a temperature aboveambient temperature.
 151. An apparatus according to claim 132 whereinsaid array of electrodes is cooled to a temperature below ambienttemperature.
 152. An apparatus according to claim 132 wherein said arrayof electrodes is replaceable.
 153. An apparatus according to claim 132further comprising means to provide neutral gas molecules within saidpulsing region for collisional cooling of said ions.
 154. A method fortrapping ions using an array of electrodes to which AC and DC voltagesare applied, and a counter electrode to which DC voltages are applied,said method comprising: (a) directing ions to a region between saidarray of electrodes and said counter electrode; and (b) applyingvoltages to said array of electrodes and said counter electrode to trapsaid ions in said region.
 155. A method according to claim 154, furthercomprising processing said ions in said trap region.
 156. A methodaccording to claim 155, wherein processing said ions comprises directingsaid ions to collide with surfaces in said trap region to producefragment ions by surface induced dissociation.
 157. A method accordingto claim 155, wherein processing said ions comprises directing said ionsto collide with surfaces in said trap region without fragmenting saidions.
 158. A method according to claim 155, wherein processing said ionscomprises the steps of directing said ions to be retained on a MALDImatrix material in said trap region; and removing said ions, ormolecules formed from said ions, using a MALDI laser pulse.
 159. Amethod according to claim 155, wherein processing said ions comprisesintroducing neutral gas molecules into said trap region to collide withsaid ions.
 160. A method for trapping ions using an array of electrodesto which AC and DC voltages are applied, and a counter electrode towhich DC voltages are applied, said method comprising: (a) producingions in a region between said array of electrodes and said counterelectrode; and (b) applying voltages to said array of electrodes andsaid counter electrode to trap said ions in said region.
 161. A methodaccording to claim 160, further comprising processing said ions in saidtrap region.
 162. A method according to claim 161, wherein processingsaid ions comprises directing said ions to collide with surfaces in saidtrap region to produce fragment ions by surface induced dissociation.163. A method according to claim 161, wherein processing said ionscomprises directing said ions to collide with surfaces in said trapregion without fragmenting said ions.
 164. A method according to claim161, wherein processing said ions comprises the steps of directing saidions to be retained on a MALDI matrix material in said trap region; andremoving said ions, or molecules formed from said ions, using a MALDIlaser pulse.
 165. A method according to claim 161, wherein processingsaid ions comprises introducing neutral gas molecules into said trapregion to collide with said ions.
 166. A method for analyzing chemicalspecies using an array of electrodes to which AC and DC voltages areapplied, a counter electrode to which DC voltages are applied, and amass spectrometer, said method comprising: (a) directing ions to aregion between said array of electrodes and said counter electrode; (b)applying voltages to said array of electrodes and said counter electrodeto trap said ions in said region; and (c) directing said ions from saidtrap region into said mass analyzer for mass-to-charge analysis.
 167. Amethod for analyzing chemical species using an array of electrodes towhich AC and DC voltages are applied, a counter electrode to which DCvoltages are applied, and a mass spectrometer, said method comprising:(a) directing ions to a region between said army of electrodes and saidcounter electrode; (b) applying voltages to said array of electrodes andsaid counter electrode to trap said ions in said region; (c) processingsaid ions in said trap region; and (d) directing said ions from saidtrap region into said mass analyzer for mass-to-charge analysis.
 168. Amethod according to claim 167, wherein processing said ions comprisesdirecting said ions to collide with surfaces in said trap region toproduce fragment ions by surface induced dissociation.
 169. A methodaccording to claim 167, wherein processing said ions comprises directingsaid ions to collide with surfaces in said trap region withoutfragmenting said ions.
 170. A method according to claim 167, whereinprocessing said ions comprises the steps of directing said ions to beretained on a MALDI matrix material in said trap region; and removingsaid ions, or molecules formed from said ions, using a MALDI laserpulse.
 171. A method according to claim 167, wherein processing saidions comprises introducing neutral gas molecules into said trap regionto collide with said ions.
 172. A method for analyzing chemical speciesusing an array of electrodes to which AC and DC voltages are applied, acounter electrode to which DC voltages are applied, and a massspectrometer, said method comprising: (a) producing ions from saidchemical species in a region between said array of electrodes and saidcounter electrode; (b) applying voltages to said array of electrodes andsaid counter electrode to trap said ions in said region; and (c)directing said ions from said trap region into said mass analyzer formass-to-charge analysis.
 173. A method for analyzing chemical speciesusing an array of electrodes to which AC and DC voltages are applied, acounter electrode to which DC voltages are applied, and a massspectrometer, said method comprising: (a) producing ions from saidchemical species in a region between said array of electrodes and saidcounter electrode; (b) applying voltages to said array of electrodes andsaid counter electrode to trap said ions in said region; (c) processingsaid ions in said trap region; and (d) directing said ions from saidtrap region into said mass analyzer for mass-to-charge analysis.
 174. Amethod according to claim 173, wherein processing said ions comprisesdirecting said ions to collide with surfaces in said trap region toproduce fragment ions by surface induced dissociation.
 175. A methodaccording to claim 173, wherein processing said ions comprises directingsaid ions to collide with surfaces in said trap region withoutfragmenting said ions.
 176. A method according to claim 1, whereinprocessing said ions comprises the steps of directing said ions to beretained on a MALDI matrix material in said trap region; and removingsaid ions, or molecules formed from said ions, using a MALDI laserpulse.
 177. A method according to claim 173, wherein processing saidions comprises introducing neutral gas molecules into said trap regionto collide with said ions.
 178. A method for analyzing chemical speciesusing a Time-of-Flight mass analyzer with an ion reflector comprising anarray of electrodes to which AC and DC voltages are applied and acounter electrode to which DC voltages are applied, said methodcomprising: (a) directing ions to a region between said array ofelectrodes and said counter electrode; (b) applying voltages to saidarray of electrodes and said counter electrode to trap said ions in saidregion; and (c) directing said ions from said trap region into saidTime-of-Flight mass analyzer for mass-to-charge analysis.
 179. A methodfor analyzing chemical species using a Time-of-Flight mass analyzer withan ion reflector comprising an array of electrodes to which AC and DCvoltages are applied and a counter electrode to which DC voltages areapplied, said method comprising: (a) directing ions to a region betweensaid array of electrodes and said counter electrode; (b) applyingvoltages to said array of electrodes and said counter electrode to trapsaid ions in said region; (c) processing said ions in said trap region;and (d) directing said ions from said trap region into saidTime-of-Flight mass analyzer for mass-to-charge analysis.
 180. A methodaccording to claim 179, wherein processing said ions comprises directingsaid ions to collide with surfaces in said trap region to producefragment ions by surface induced dissociation.
 181. A method accordingto claim 179, wherein processing said ions comprises directing said ionsto collide with surfaces in said trap region without fragmenting saidions.
 182. A method according to claim 179, wherein processing said ionscomprises the steps of directing said ions to be retained on a MALDImatrix material in said trap region; and removing said ions, ormolecules formed from said ions, using a MALDI laser pulse.
 183. Amethod according to claim 179, wherein processing said ions comprisesintroducing neutral gas molecules into said trap region to collide withsaid ions.
 184. A method for analyzing chemical species using aTime-of-Flight mass spectrometer comprising a pulsing region and adetector, said pulsing region comprising an array of electrodes to whichAC and DC voltages are applied and a counter electrode to which DCvoltages are applied, said method comprising: (a) operating an ionsource to produce ions; (b) processing said ions and delivering saidprocessed ions to the region between said array of electrodes and saidcounter electrode; (c) applying voltages to said array of electrodes andsaid counter electrode to trap said processed ions in said region; (d)directing said processed ions from said trap region into saidTime-of-Flight mass analyzer for mass-to-charge analysis.
 185. A methodaccording to claim 184, wherein processing said ions comprisesfragmenting said ions by gas phase collision induced dissociation. 186.A method according to claim 184, wherein processing said ions comprisesmass-to-charge selecting said ions.
 187. A method according to claim184, wherein processing said ions comprises fragmenting andmass-to-charge selecting said ions.
 188. A method according to claim184, wherein processing said ions comprises mass-to-charge selecting andfragmenting said mass-to-charge selected ions.
 189. A method accordingto claim 184 wherein processing said ions comprises trapping andreleasing said ions.
 190. A method for analyzing chemical species usinga Time-of-Flight mass spectrometer comprising a pulsing region and adetector, said pulsing region comprising an array of electrodes to whichAC and DC voltages are applied and a counter electrode to which DCvoltages are applied, said method comprising: (a) operating an ionsource to produce ions; (b) processing said ions and delivering saidprocessed ions to the region between said array of electrodes and saidcounter electrode; (c) applying voltages to said array of electrodes andsaid counter electrode to trap said processed ions in said region; (d)processing said processed ions in said trap region; and (e) directingsaid processed ions from said trap region into said Time-of-Flight massanalyzer for mass-to-charge analysis.
 191. A method according to claim190, wherein processing said ions comprises fragmenting said ions by gasphase collision induced dissociation.
 192. A method according to claim190, wherein processing said ions comprises mass-to-charge selectingsaid ions.
 193. A method according to claim 190, wherein processing saidions comprises fragmenting and mass-to-charge selecting said ions. 194.A method according to claim 190, wherein processing said ions comprisesmass-to-charge selecting and fragmenting said mass-to-charge selectedions.
 195. A method according to claim 190, wherein processing said ionscomprises trapping and releasing said ions.
 196. A method according toclaim 190, wherein processing said processed ions comprises directingsaid ions to collide with surfaces in said trap region to producefragment ions by surface induced dissociation.
 197. A method accordingto claim 190, wherein processing said processed ions comprises directingsaid ions to collide with surfaces in said trap region withoutfragmenting said ions.
 198. A method according to claim 190, whereinprocessing said processed ions comprises the steps of directing saidions to be retained on a MALDI matrix material in said trap region; andremoving said ions, or molecules formed from said ions, using a MALDIlaser pulse.
 199. A method according to claim 190, wherein processingsaid processed ions comprises introducing neutral gas molecules intosaid trap region to collide with said ions.